NL2036594B1

NL2036594B1 - Bacterium comprising phytate-degradation pathway

Info

Publication number: NL2036594B1
Application number: NL2036594A
Authority: NL
Inventors: Meindert De Vos Willem; Nieuwdorp Max; Phuong Nam Bui Thi
Original assignee: Univ Wageningen; Acad Medisch Ct
Priority date: 2023-12-20
Filing date: 2023-12-20
Publication date: 2025-07-04
Also published as: WO2025132829A1

Abstract

The invention is concerned with a bacterium comprising a phytate to 3-hydroxoypropionate pathway gene set that allows said bacterium to convert phytate to 3-hydroxypropionate or a salt or ester thereof. The bacterium can be used as a probiotic or supplement to promote production of propionate in the GI tract, thereby preventing and/or treating conditions or diseases that benefit from the production of propionate, for example metabolic disease, metabolic syndrome, obesity, insulin resistance or insulin resistance-related conditions, particularly dyslipidemia, (M)ASLD-(M)ASH, type 2 diabetes mellitus and insulin-resistance in endocrine diseases.

Description

P36534NL0O0/MJO

Bacterium comprising phytate-degradation pathway

Technical field

The present invention relates to the field of preventing and/or treating metabolic diseases, such as metabolic syndrome and insulin resistance or insulin resistance-related conditions, including dyslipidemia and type 2 diabetes mellitus as well as insulin-resistance in endocrine diseases or obesity.

Background of the disclosure

Phytate, a well-known phytochemical, is widely distributed in the plant kingdom, and especially abundant in wheat, rice and nuts. Dietary supplementation of phytate has been reported for various health benefits, including anti-diabetic activity.

In particular, dietary phytate supplementation reportedly promotes epithelial repair resulting in improved gut barrier function (Wu et al., Nature 2020, 586 (7827), 108-112), reduces serum levels of glycated hemoglobin HbA1c and Advanced Glycation End products (Sanchis et al., Trial. Sci. Rep. 2018, 8 91), 9619), improves glucose metabolism (Lee et al.,

Nutr Res 20086, 26(9), 474-479), reduced inflammation (Liu et al., Br J. Nutr 2018, 120(2), 121-130) and exerts protective effects against colon cancer (Vucenik et al., Nutr Cancer 20086, 55(2), 109-25).

However, the molecular mechanism by which dietary phytate confers its health benefits is largely unknown. It was recently reported that under anaerobic conditions, the human fecal microbiome is able to fully convert phytate into short-chain fatty acids (SCFAs), including propionate and butyrate (Bui et al., Nat. Commun 2021, 12(1), 4798), which are well known microbial signaling molecules and strongly associated with host health. Nevertheless, the microbes responsible for metabolizing phytate in the human gut are unknown. Previous efforts to detect and cultivate phytate-degrading microbes from human fecal samples have remained unsuccessful (Curr Issues Intest Microbiol. 2004 Sep;5(2):23-39). This contrasts with animal studies that identified phytase-producing Mitsuokella spp. in ruminants (Haros et al., FEMS Microbiology Letters, 2005, 247(2), 231-239). Mitsuokelfa spp. are Gram-negative gut anaerobes belonging to the Negativicutes and the rumen isolate M. multacida possesses a phytase that is located in the outer membrane (d'Silva et al., Can J Microbiol 2000, 46(4), 391-5).

There remains a need to unravel how dietary phytate is metabolized by human gut bacteria and in the human gut and to identify their phytate degradation pathway. It is an objective of the present disclosure to provide a new or improved strategy for obtaining the health benefits of phytate. In particular, it is an objective of the present invention, to provide for new means for preventing and/or treating metabolic diseases, in particular metabolic syndrome and insulin resistance or insulin resistance-related conditions, including dyslipidemia and type 2 diabetes mellitus as well as insulin-resistance in endocrine diseases (e.g., obese subjects with type 1 diabetes mellitus, Cushing's disease or lipodystrophy syndromes).

Summary of the disclosure

The present inventors identified Mitsuokella jalaludinii as an efficient phytate degrader in the human gut. Subsequently, a complete phytate degradation pathway in Mitsuokella jalaludinii was elucidated with NMR spectroscopy using 13C-isotope labelling and transcriptomic and genomic analysis. The genes involved in the pathway are disclosed herein and can be introduced in any suitable host bacterium to achieve phytate degradation activity.

The host bacterium may, for example, be Escherichia coli, Bifidobacterium spp., Lactobacillus spp. Lactococcus spp., or Lactobacillus spp.

A major end product of the pathway is the antimicrobial 3-hydroxypropionate. In addition, it was found that 3-hydroxypropionate can be converted into propionate in a synergistic interaction with Anaerostipes rhamnosivorans both in vitro and in vivo. The pathway for converting 3-hydroxypropionate into propionate has also been unravelled.

Furthermore, it has been found that the supernatant of the phytate-digesting coculture of

Mitsuokella jalaludinii and Anaerostipes rhamnosivorans leads to an improved intestinal barrier integrity via activating tight junction genes. These results suggest that the conversion of phytate to propionate by Mitsuokella jalaludinii and optionally Anaerostipes rhamnosivorans is responsible for phytate-driven health benefits.

The present inventors envisage supplementation of a subject with a bacterium according to the present disclosure, or the synergistic combination of bacteria according to the present disclosure, to provide for a direct or synergistic effect via in situ (3-hydroxy)propionate production.

Detailed description of the disclosure

The present disclosure relates to a first bacterium comprising a gene set encoding a pathway for the conversion of phytate to 3-hydroxypropionate or a salt or ester thereof that allows said bacterium to convert phytate to 3-hydroxypropionate or a salt or ester thereof, for use in preventing and/or treating metabolic syndrome, insulin resistance and/or insulin resistance related condition.

Specifically, the bacterium is capable of converting phytate into 3-hydroxypropionate or a derivative thereof via phytate metabolism and 3-hydroxypropionate synthesis. The term phytate is well-known to the skilled person and can be interchangeable with the terms myo-inositol-hexakisphosphate or myo-inositol-1,2,3,4,5,6-hexakisphosphate or InsPs.

In addition, the present disclosure relates to a second bacterium comprising a gene set encoding a pathway for the conversion of 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof that allows said bacterium to convert 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof, for use in preventing and/or treating metabolic syndrome, insulin resistance and/or insulin resistance related condition.

Also foreseen is to combine the gene set of the first bacterium and the gene set of the second bacterium, e.g. in a single bacterium. Accordingly, provided is a bacterium that comprises a gene set encoding a pathway for the conversion of phytate to 3- hydroxypropionate or a salt or ester thereof and a gene set encoding a pathway for the conversion of 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof, that allows said bacterium to convert phytate to propionate or a salt or ester thereof, for example for use in preventing and/or treating metabolic syndrome, insulin resistance and/or insulin resistance related condition.

The bacteria according to the present disclosure (or strains derived therefrom), when administered to a human being or when ingested by a human being in an adequate amount, are able to survive and at least transiently colonize the gastrointestinal (Gl) tract of said human being. Colonization of the first bacterium enables greater in situ production of 3- hydroxypropionate and together with colonization of the second bacterium greater in situ production of propionate is enabled. Increased in situ production of 3-hydroxypropionate and/or propionate is believed to underlie beneficial effects as taught herein, e.g. preventing and/or treating conditions or diseases such as metabolic diseases, such as metabolic syndrome and insulin resistance or insulin resistance-related complications, such as dyslipidemia and type 2 diabetes mellitus as well as insulin-resistance in endocrine diseases (e.g., obese subjects with type 1 diabetes mellitus, Cushing's disease or lipodystrophy syndromes).

Bacterium

In a first aspect, the present disclosure relates to a first bacterium comprising a gene set encoding a pathway for the conversion of phytate to 3-hydroxypropionate or a salt or ester thereof that allows said bacterium to convert phytate to 3-hydroxypropionate or a salt or ester thereof, in particular but not necessarily under anaerobic conditions, such as wherein the bacterium and/or its medium is not in contact with gas comprising more than 0.1 vol%, 1 volt, 2 vol%, 3 vol%, 4 vol%, 5 vol%, or 10 vol% of oxygen. The bacterial strain is preferably, but not necessarily, an isolate, e.g. a human intestinal isolate.

The phytate to 3-hydroxypropionate or a salt or ester thereof pathway gene set may comprise one or more (e.9g., at least two or three, or all} of the genes encoding the proteins: phytase, major myo-inositol transporter lolT, myo-inositol 2-dehydrogenase, inosose dehydratase, 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase, 5-deoxy-glucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase, 2-hydroxy-3-oxopropionate reductase, D-beta-hydroxypropionate permease.

Additionally, the phytate to 3-hydroxypropionate or a salt or ester thereof pathway gene set may comprise the gene(s) encoding the proteins phosphate ABC transporter PstS,

Phosphate ABC transporter PstC, Phosphate ABC transporter PstA, Na+/H+ antiporter NhaA type, phosphoglycerate mutase, triosephosphate isomerase, enolase, phosphoglycerate kinase, pyruvate kinase, NAD-dependent glyceraldehyde-3-phosphate dehydrogenase,

D-lactate dehydrogenase, pyruvate-flavodoxin oxidoreductase, acetyl-CoA hydrolase,

D-lactate dehydrogenase, pyruvate carboxylase, malate dehydrogenase, NADP-dependent malic enzyme, fumarate hydratase alpha subunit, fumarate hydratase beta subunit, succinate dehydrogenase cytochrome b558 subunit, succinate dehydrogenase flavoprotein subunit, succinate dehydrogenase iron-sulfur protein and/or ATP synthase epsilon chain_MJ_0869,

ATP synthase beta chain, ATP synthase gamma chain, ATP synthase alpha chain, ATP synthase delta chain, ATP synthase FO sector subunit b, ATP synthase FO sector subunit Cc,

ATP synthase FO sector subunit a, and/or ATP synthase protein I.

In a preferred embodiment, at least one (or at least two or three or all) of the proteins: phytase, major myo-inositol transporter lolT, myo-inositol 2-dehydrogenase, inosose dehydratase, 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase, 5-deoxy-glucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase, 2-hydroxy-3-oxopropionate reductase, D-beta-hydroxypropionate permease, phosphate ABC transporter PstS, Phosphate ABC transporter PstC, Phosphate ABC transporter PstA,

Na+/H+ antiporter NhaA type, phosphoglycerate mutase, triosephosphate isomerase, enolase, phosphoglycerate kinase, pyruvate kinase, NAD-dependent glyceraldehyde-3-phosphate dehydrogenase, D-lactate dehydrogenase, pyruvate-flavodoxin oxidoreductase, acetyl-CoA hydrolase, D-lactate dehydrogenase, pyruvate carboxylase, malate dehydrogenase, NADP-dependent malic enzyme, fumarate hydratase alpha subunit, fumarate hydratase beta subunit, succinate dehydrogenase cytochrome b558 subunit, succinate dehydrogenase flavoprotein subunit, succinate dehydrogenase iron-sulfur protein,

ATP synthase epsilon chain, ATP synthase beta chain, ATP synthase gamma chain, ATP synthase alpha chain, ATP synthase delta chain, ATP synthase FO sector subunit b, ATP synthase FO sector subunit c‚ ATP synthase FO sector subunit a, and/or ATP synthase protein | may be overproduced (or the genes encoding therefor overexpressed) when the bacterium is grown in the presence of phytate as compared to when the bacterium is grown in the absence of phytate.

In the context of the present disclosure, the amount of phytate used to determine whether genes are upregulated or proteins are overexpressed in a bacterium as compared to when said bacterium is grown in absence of phytate may be in the range of from about 5 mM to about 100 mM, preferably from about 10 mM to about 50 mM, more preferably from about 15 mM to about 25 mM, and even more preferably about 20 mM.

In an embodiment, the first bacterium according to the present disclosure may be an isolated intestinal bacterial strain, or strain derived therefrom, and/or may be an intestinal bacterium isolated from a human being, which naturally comprises an phytate to 3- hydroxypropionate or a salt or ester pathway gene set as taught herein and which is capable of converting phytate to 3-hydroxypropionate or a salt or ester (or a derivative) thereof.

In a further aspect, the first bacterium according to the disclosure may be a Mitsuokella species, preferably Mitsuokella jalaludinii or relative thereof or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:93. In particular, the first bacterium may be Mitsuokella jalaludinii H1-1 deposited by Wageningen University on December 1, 2023 at the Westerdijk Fungal Biodiversity Institute (CBS) located at

Uppsalalaan 8, 3584CT Utrecht, the Netherlands, assigned the deposit number CBS 150836.

Also encompassed is any bacterial strain derived from the deposited bacterium.

Alternatively, the first bacterium according to the present disclosure may be a bacterium which has been transfected with the phytate to 3-hydroxypropionate or a salt or ester thereof pathway gene set as taught herein, and which is capable of converting phytate to 3-hydroxypropionate or a salt or ester (or a derivative) thereof. The skilled person is well-acquainted with methods for transforming bacteria with a desired genetic construct (i.e. pathway gene set).

In a second aspect, the present disclosure relates to a (second) bacterium comprising a gene set encoding a pathway for conversion of 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof that allows said second bacterium to convert 3- hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof, in particular but not necessarily under anaerobic conditions, such as wherein the bacterium and/or its medium is not in contact with gas comprising more than 1 vol%, 2 vol%, 3 vol%, 4 vol%, 5 vol%, or 10 vol% of oxygen. The bacterial strain is preferably, but not necessarily, an isolate, e.g. a human intestinal isolate.

The 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof pathway gene set may comprise one or more (e.g., at least two or three, or all) of the genes encoding the proteins: permease, oxoacid CoA transferase, dehydratase, electron transfer flavoprotein beta subunit, electron transfer flavoprotein alpha subunit, and/or acyl dehydrogenase.

Additionally, the 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof pathway gene set may comprise the genes encoding the proteins ATP synthase epsilon chain, ATP synthase beta chain, ATP synthase gamma chain, ATP synthase alpha chain, ATP synthase delta chain, ATP synthase FO sector subunit b, ATP synthase FO sector subunit ¢, ATP synthase FO sector subunit a, and/or ATP synthase protein |.

Preferably, the first bacterium as disclosed herein is combined with the second bacterium as disclosed herein. Preferably, the first bacterium and/or second bacterium as disclosed herein are live bacteria. Preferably, the first bacterium and/or second bacterium as disclosed herein have (machinery for} ATP production and/or NADH production.

In a preferred embodiment, at least one (or at least two or three or all) of the proteins: permease, oxoacid CoA transferase, dehydratase, electron transfer flavoprotein, beta subunit, electron transfer flavoprotein, alpha subunit, and/or acyl dehydrogenase, ATP synthase epsilon chain, ATP synthase beta chain, ATP synthase gamma chain, ATP synthase alpha chain, ATP synthase delta chain, ATP synthase FO sector subunit b, ATP synthase FO sector subunit ¢, ATP synthase FO sector subunit a, and/or ATP synthase protein | may be overproduced (or the genes encoding therefor overexpressed) when the bacterium is grown in the presence of 3-hydroxypropionate as compared to when the (second) bacterium is grown in the absence of 3-hydroxypropionate.

In the context of the present disclosure, the amount of 3-hydroxypropionate used to determine whether genes are upregulated or proteins are overexpressed in a bacterium as compared to when said bacterium is grown in absence of 3-hydroxypropionate may be in the range of from about 5 mM to about 100 mM, preferably from about 10 mM to about 50 mM, more preferably from about 15 mM to about 25 mM, and even more preferably about 20 mM.

In an embodiment, the (second) bacterium according to the present disclosure may be an isolated intestinal bacterial strain, or strain derived therefrom, and/or may be an intestinal bacterium isolated from a human being, which naturally comprises a 3-hydroxypropionate or a salt or ester to propionate or salt or ester thereof pathway gene set as taught herein and which is capable of converting 3-hydroxypropionate or a salt or ester (or a derivative) thereof to propionate or a salt or ester (or derivative) thereof.

In a further aspect, the (second) bacterium according to the disclosure may be an

Anaerostipes species (which has ability to convert 3-hydroxypropionate to propionate), although preferably not Anaerostipes butyraticus (e.g. DSM22094T) but for example

Anaerostipes caccae (e.g. DSM14662) or Anaerostipes hadrus (preferably PEL85, but preferably not DSM3319T, and/or preferably not DSM108065). Particularly preferred is

Anaerostipes rhamnosivorans (1y2) or relative thereof or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:94. In particular, the first bacterium may be Anaerostipes rhamnosivorans 1y2 deposited by Wageningen

University on June 26, 2015 at the Centraalbureau voor Schimmelcultures (now named

Westerdijk Fungal Biodiversity Institute) located at Uppsalalaan 8, 3584CT Utrecht, the

Netherlands, assigned the deposit number CBS 140182.

Alternatively, the (second) bacterium according to the present disclosure may be a bacterium which has been transfected with the 3-hydroxypropionate or a salt or ester thereof to propionate or salt or ester thereof pathway gene set as taught herein, and which is capable of converting 3-hydroxypropionate or a salt or ester (or a derivative) thereof to propionate or a salt or ester (or derivative) thereof. The skilled person is well-acquainted with methods for transforming bacteria with a desired genetic construct (i.e. pathway gene set).

The phytate to 3-hydroxypropionate or a salt or ester thereof pathway gene set

The gene encoding phytase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:1. Additionally or alternatively, the gene encoding phytase may encode a phytase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:2. The function of the gene phytase can be seen in the conversion of phytate to (myo-)inositol and phosphate.

The gene encoding major myo-inositol transporter lolT may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:3. Additionally or alternatively, the gene encoding major myo-inositol transporter lolT may encode a major myo-inositol transporter [oIT that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with

SEQ ID NO:4. The function of the gene major myo-inositol transporter lolT can be seen in the transport of inositol (across the cell membrane).

The gene encoding myo-inositol 2-dehydrogenase may have at least 70, 80, 90, 95, 99, 100% sequence identity with SEQ ID NO:45. Additionally or alternatively the gene encoding myo-inositol 2-dehydrogenase may encode an myo-inositol 2-dehydrogenase that has at least 70, 80, 90, 95, 99, 100% sequence identity with SEQ ID NO:46. The function of the gene myo-inositol 2-dehydrogenase can be seen in the conversion of myo-inositol to scyllo- inosose.

The gene encoding inosose dehydratase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:5. Additionally or alternatively, the gene encoding inosose dehydratase may encode an inosose dehydratase that has at least 70%, 80%, 90%, 95%, 99%, or 100%sequence identity with SEQ ID NO: 6. The function of the gene inosose dehydratase can be seen in the conversion of scyllo-inosose to 3,5/4-trihydroxycyclohexa- 1,2-dione.

The gene encoding 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase may have at least 70%, 80%, 80%, 95%, 99%, or 100% sequence identity with SEQ ID NO:7. Additionally or alternatively, the gene encoding 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase may encode an 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:8. The function of the gene 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase can be seen in the conversion of 3,5/4-trihydroxycyclohexa-1,2-dione to 5-deoxy-D-glucuronate.

The gene encoding 5-deoxy-glucuronate isomerase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:9. Additionally or alternatively, the gene encoding 5-deoxy-glucuronate isomerase may encode a 5-deoxy-glucuronate isomerase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ

ID NO:10. The function of the gene 5-deoxy-glucuronate isomerase can be seen in the conversion of 5-deoxy-D-glucuronate to 2-deoxy-5-keto-D-gluconate.

The gene encoding 5-keto-2-deoxygluconokinase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:11. Additionally or alternatively, the gene encoding 5-keto-2-deoxygluconokinase may encode a 5-keto-2-deoxygluconokinase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:12.

The function of the gene 5-keto-2-deoxygluconokinase can be seen in the conversion of 2- deoxy-5-keto-D-gluconate to 2-deoxy-5-keto-D-gluconate-6P.

The gene encoding 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:13. Additionally or alternatively, the gene encoding 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase may encode a 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:14. The function of the gene 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase can be seen in the conversion of 5-dehydro-2-deoxy-D- Gluconate-6-phosphate to 3-oxopropionate (and/or in the conversion of 5-dehydro-2-deoxy-D- Gluconate-6-phosphate to glycerone phosphate).

The gene encoding 2-hydroxy-3-oxopropionate reductase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:15. Additionally or alternatively, the gene encoding 2-hydroxy-3-oxopropionate reductase may encode a 2-hydroxy-3- oxopropionate reductase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:16. The function of the gene 2-hydroxy-3-oxopropionate reductase can be seen in the conversion of 3-oxopropionate to 3-hydroxypropionate.

The gene encoding D-beta-hydroxypropionate permease may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:17. Additionally or alternatively, the gene encoding D-beta-hydroxypropionate permease may encode a D-beta- hydroxypropionate permease that has at least 70%, 80%, 90%, 95%, 99%, or 100%

sequence identity with SEQ ID NO:18. The function of the gene D-beta-hydroxypropionate permease can be seen in 3-hydroxypropionate transport (across cell membrane).

The gene encoding phosphate ABC transporter PstS may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO: 19. Additionally or alternatively, the gene encoding phosphate ABC transporter PstS may encode a phosphate ABC transporter

PstS that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID

NO:20. The function of the gene phosphate ABC transporter PstS can be seen in the transport of phosphate (across the cell membrane).

The gene encoding Phosphate ABC transporter PstC may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:21. Additionally or alternatively, the gene encoding Phosphate ABC transporter PstC may encode a Phosphate ABC transporter

PstC that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID

NO:22. The function of the gene Phosphate ABC transporter PstC can be seen in the transport of phosphate (across the cell membrane).

The gene encoding Phosphate ABC transporter PstA may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:23. Additionally or alternatively, the gene encoding Phosphate ABC transporter PstA may encode a Phosphate ABC transporter

PstA that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID

NO:24. The function of the gene Phosphate ABC transporter PstA can be seen in the transport of phosphate (across the cell membrane).

The gene encoding Na+/H+ antiporter NhaA type may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:25. Additionally or alternatively, the gene encoding Na+/H+ antiporter NhaA type may encode a Na+/H+ antiporter NhaA type that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:26. The function of the gene Na+/H+ antiporter NhaA type can be seen in the transport of phosphate (across the cell membrane).

The gene encoding phosphoglycerate mutase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:27. Additionally or alternatively, the gene encoding phosphoglycerate mutase may encode a phosphoglycerate mutase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:28.

The gene encoding triosephosphate isomerase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:29. Additionally or alternatively, the gene encoding triosephosphate isomerase may encode a triosephosphate isomerase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:30.

The gene encoding enolase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:31. Additionally or alternatively, the gene encoding enolase may encode an enolase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:32.

The gene encoding phosphoglycerate kinase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:33. Additionally or alternatively, the gene encoding Phosphoglycerate kinase may encode a phosphoglycerate kinase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:34.

The gene encoding pyruvate kinase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:35. Additionally or alternatively, the gene encoding pyruvate kinase may encode a pyruvate kinase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:36.

The gene encoding NAD-dependent glyceraldehyde-3-phosphate dehydrogenase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:37.

Additionally or alternatively, the gene NAD-dependent glyceraldehyde-3-phosphate dehydrogenase may encode a NAD-dependent glyceraldehyde-3-phosphate dehydrogenase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:38.

The function of the gene NAD-dependent glyceraldehyde-3-phosphate dehydrogenase can be seen in the conversion of glycerone phosphate to pyruvate.

The gene encoding D-lactate dehydrogenase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:39. Additionally or alternatively, the gene D- lactate dehydrogenase may encode a D-lactate dehydrogenase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:40. The function of the gene D- lactate dehydrogenase can be seen in the conversion of pyruvate to lactate.

The gene encoding pyruvate-flavodoxin oxidoreductase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:41. Additionally or alternatively, the gene pyruvate-flavodoxin oxidoreductase may encode an pyruvate-flavodoxin oxidoreductase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with

SEQ ID NO:42. The function of the gene pyruvate-flavodoxin oxidoreductase can be seen in the conversion of pyruvate to acetyl-CoA.

The gene encoding acetyl-CoA hydrolase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:43. Additionally or alternatively, the gene acetyl-

CoA hydrolase may encode an acetyl-CoA hydrolase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:44. The function of the gene acetyl-CoA hydrolase can be seen in the conversion of acetyl-CoA to acetate.

The gene encoding D-lactate dehydrogenase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:45. Additionally or alternatively, the gene D- lactate dehydrogenase may encode an D-lactate dehydrogenase that has at least 70%, 80%,

90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:46. The function of the gene D- lactate dehydrogenase can be seen in the conversion of pyruvate to lactate.

The gene encoding pyruvate carboxylase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:47. Additionally or alternatively, the gene pyruvate carboxylase may encode a pyruvate carboxylase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:48. The function of the gene pyruvate carboxylase can be seen in the conversion of pyruvate to oxaloacetate.

The gene encoding malate dehydrogenase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:49. Additionally or alternatively, the gene malate dehydrogenase may encode a malate dehydrogenase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:50. The function of the gene malate dehydrogenase can be seen in the conversion of oxaloacetate to malate.

The gene encoding NADP-dependent malic enzyme may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:51. Additionally or alternatively, the gene NADP-dependent malic enzyme may encode an NADP-dependent malic enzyme that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:52. The function of the gene NADP-dependent malic enzyme can be seen in the conversion of pyruvate to malate.

The gene encoding fumarate hydratase alpha subunit may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:53. Additionally or alternatively, the gene fumarate hydratase alpha subunit may encode an fumarate hydratase alpha subunit that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:54.

The function of the gene fumarate hydratase alpha subunit can be seen in the conversion of malate to fumarate.

The gene encoding fumarate hydratase beta subunit may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:55. Additionally or alternatively, the gene fumarate hydratase beta subunit may encode an fumarate hydratase beta subunit that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:56. The function of the gene fumarate hydratase beta subunit can be seen in the conversion of malate to fumarate.

The gene encoding succinate dehydrogenase cytochrome b558 subunit may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:57. Additionally or alternatively, the gene succinate dehydrogenase cytochrome b558 subunit may encode an succinate dehydrogenase cytochrome b558 subunit that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:58. The function of the gene succinate dehydrogenase cytochrome b558 subunit can be seen in the conversion of fumarate to succinate

The gene encoding succinate dehydrogenase flavoprotein subunit may have at least 70%, 80%, 90%, 95%, 89%, or 100% sequence identity with SEQ ID NO:59. Additionally or alternatively, the gene succinate dehydrogenase flavoprotein subunit may encode an succinate dehydrogenase flavoprotein subunit that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:60. The function of the gene succinate dehydrogenase flavoprotein subunit can be seen in the conversion of fumarate to succinate

The gene encoding succinate dehydrogenase iron-sulfur protein may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:61. Additionally or alternatively, the gene succinate dehydrogenase iron-sulfur protein may encode an succinate dehydrogenase iron-sulfur protein that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:62. The function of the gene succinate dehydrogenase iron-sulfur protein can be seen in the conversion of fumarate to succinate

The gene encoding ATP synthase epsilon chain may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:63. Additionally or alternatively, the gene

ATP synthase epsilon chain may encode an ATP synthase epsilon chain that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:64.

The gene encoding ATP synthase beta chain may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:65. Additionally or alternatively, the gene

ATP synthase beta chain may encode an ATP synthase beta chain that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:66.

The gene encoding ATP synthase gamma chain may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:67. Additionally or alternatively, the gene

ATP synthase gamma chain may encode an ATP synthase gamma chain that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:68.

The gene encoding ATP synthase alpha chain may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:68. Additionally or alternatively, the gene

ATP synthase alpha chain may encode an ATP synthase alpha chain that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:70.

The gene encoding ATP synthase delta chain may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:71. Additionally or alternatively, the gene

ATP synthase delta chain may encode an ATP synthase delta chain that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:72.

The gene encoding ATP synthase FO sector subunit b may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:73. Additionally or alternatively, the gene ATP synthase FO sector subunit b may encode an ATP synthase FO sector subunit b that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:74.

The gene encoding ATP synthase FO sector subunit c may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:75. Additionally or alternatively, the gene ATP synthase FO sector subunit ¢ may encode an ATP synthase FO sector subunit c that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:76.

The gene encoding ATP synthase FO sector subunit a may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:77. Additionally or alternatively, the gene ATP synthase FO sector subunit a may encode an ATP synthase FO sector subunit a that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:78.

The gene encoding ATP synthase protein | may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:79. Additionally or alternatively, the gene ATP synthase protein | may encode an ATP synthase protein | that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:80.

The 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof pathway gene set

The gene encoding permease may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:81. Additionally or alternatively, the gene permease may encode a permease that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:82. The function of the gene permease can be seen in the transport of 3- hydroxypropionate (across the cell membrane).

The gene encoding oxoacid CoA transferase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:83. Additionally or alternatively, the gene oxoacid CoA transferase may encode an oxoacid CoA transferase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:84. The function of the gene oxoacid CoA transferase can be seen in the conversion of 3-hydroxypropionate to 3- hydroxy propionyl-CoA.

The gene encoding dehydratase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:85. Additionally or alternatively, the gene dehydratase may encode an dehydratase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:86. The function of the gene dehydratase can be seen in the conversion of 3-hydroxy propionyl-CoA to Acryloyl-CoA.

The gene encoding electron transfer flavoprotein beta subunit may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:87. Additionally or alternatively, the gene electron transfer flavoprotein beta subunit may encode an electron transfer flavoprotein beta subunit that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:88. The function of the gene electron transfer flavoprotein beta subunit can be seen in the conversion of acryloyl-CoA to propionyl-Coa.

The gene encoding electron transfer flavoprotein alpha subunit may have at least 70%, 80%, 90%, 95%, 89%, or 100% sequence identity with SEQ ID NO:86. Additionally or alternatively, the gene electron transfer flavoprotein alpha subunit may encode an electron transfer flavoprotein alpha subunit that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:90. The function of the gene electron transfer flavoprotein alpha subunit can be seen in the conversion of acryloyl-CoA to propionyl-Coa.

The gene encoding acyl dehydrogenase may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:91. Additionally or alternatively, the gene acyl dehydrogenase may encode an acyl dehydrogenase that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:92. The function of the gene acyl dehydrogenase can be seen in the conversion of acryloyl-CoA to propionyl-Coa..

ATP synthase beta chain may encode an ATP synthase beta chain that has at least 70%, 80%, 90%, 95%, 89%, or 100% sequence identity with SEQ ID NO:66.

The gene encoding ATP synthase gamma chain may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:87. Additionally or alternatively, the gene

The gene encoding ATP synthase alpha chain may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:69. Additionally or alternatively, the gene

ATP synthase alpha chain may encode an ATP synthase alpha chain that has at least 70%, 80%, 90%, 95%, 89%, or 100% sequence identity with SEQ ID NO:70.

The gene encoding ATP synthase FO sector subunit c may have at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:75. Additionally or alternatively, the gene ATP synthase FO sector subunit c may encode an ATP synthase FO sector subunit ¢ that has at least 70%, 80%, 90%, 95%, 99%, or 100% sequence identity with SEQ ID NO:76.

Compositions

The present disclosure provides a kit comprising a composition comprising the first bacterium and/or a composition comprising the second bacterium, wherein optionally the compositions comprise a physiologically acceptable carrier. The present disclosure also provides a composition comprising the first bacterium and/or second bacterium according to the present disclosure and optionally a physiologically acceptable carrier. The physiologically acceptable carrier may be any carrier that is suitable for keeping the bacterium/bacteria as taught herein viable until consumption by a subject (e.g. human or animal). Non-limiting examples of acceptable carriers that are suitable for this purpose include any well-known physiological or pharmaceutical carriers, buffers, and excipients. It will be appreciated that the choice of a suitable physiological or pharmaceutical carrier will depend upon the intended mode of administration of the composition as taught herein (e.g. oral) and the intended form of the composition (e.g. beverage, yogurt, powder, capsules, and the like}. The skilled person knows how to select a physiological or pharmaceutical carrier, which is suitable for the compositions as taught herein.

In an embodiment, the composition as taught herein may be in the form of a food composition, feed composition, feed supplement composition, food supplement composition or pharmaceutical composition. The composition is preferably suitable for consumption by a human being.

In an embodiment, the composition is a food or food supplement composition. The food or food supplement composition may be selected from the group consisting of a liquid, liquid beverage (including dairy beverage and fermented beverage), yogurt, cheese, gel, gelatine, gelatine capsule, powder, paste, pressed tablet, and gel cap. In a suitable embodiment, the composition is a liquid, preferably a liquid beverage (e.g. dairy beverage). The food or food supplement composition may be a dairy product, preferably a fermented dairy product, such as yogurt or yogurt drink.

In an embodiment, the composition as taught herein may be a probiotic composition. Such probiotic composition may comprise the first (isolated) bacterium and/or second (isolated) bacterium as taught herein, or a strain derived therefrom. In an embodiment, the composition as taught herein further comprises one or more additional beneficial isolated intestinal bacterial strain.

In an embodiment, the composition may be a symbiotic composition. It may be advantageous to add one or more prebiotic ingredients to the composition as taught herein, for example, to supplement the effects (e.g. production of 3-hydroxypropionate/propionate} of the first bacterium and/or second bacterium as taught herein.

In an embodiment, the one or more prebiotic ingredients may be any prebiotic ingredients, which are suitable to enhance the activity and/or stimulate the growth of the bacterium, or a strain derived therefrom, as taught herein. Non-limiting examples of suitable prebiotic ingredients include fibres such as inulin, pectin, and resistant starch, as well as cellobiose, maltose, mannose, salicine, trehalose, amygdalin, arabinose, melibiose, sorbitol, rhamnose and xylose.

In an embodiment, the composition as taught herein comprises a phytate-rich source and/or phytate. For instance, it may be advantageous to add a phytate-rich source and/or phytate to the composition as taught herein to further promote the production of 3-hydroxypropionate/propionate or a derivative thereof in the GI tract of a mammal (e.g. human being).

In an embodiment, the composition as taught herein may comprise one or more ingredients which are suitable for promoting survival and/or viability of the bacterium or strain derived therefrom as taught herein during storage and/or during exposure to bile and/or during passage through the Gl tract of a mammal (e.g. a human being). Non-limiting examples of such ingredients include an enteric coating and controlled release agents allowing passage through the stomach. The skilled person knows how to select suitable ingredients for maintaining a bacterium as taught herein viable and functional, i.e. able to carry out intended function(s).

In one embodiment, the compositions as taught herein may further comprise one or more ingredients, which further enhance the nutritional value and/or the therapeutic value the compositions as taught herein. For instance, it may be advantageous to add one or more ingredients (e.g. nutritional ingredients, veterinary, medicinal agents, etc.) selected from the group consisting of proteins, amino acids, enzymes, mineral salts, vitamins (e.g. thiamine

HCI, riboflavin, pyridoxine HCI, niacin, inositol, choline chloride, calcium pantothenate, biotin, folic acid, ascorbic acid, vitamin B12, p-aminobenzoic acid, vitamin A acetate, vitamin K, vitamin D, vitamin E, and the like), sugars and complex carbohydrates (e.g. water-soluble and water-insoluble monosaccharides, disaccharides, and polysaccharides), medicinal compounds (e.g. antibiotics), antioxidants, and trace element ingredients (e.g. compounds of cobalt, copper, manganese, iron, zinc, tin, nickel, chromium, molybdenum, iodine, chlorine, silicon, vanadium, selenium, calcium, magnesium, sodium and potassium and the like). The skilled person is familiar with methods and ingredients that are suitable to enhance the nutritional and/or therapeutic/medicinal value of the compositions as taught herein.

The first bacterium and/or second bacterium as taught herein may be incorporated into the composition in lyophilized form, microencapsulated form (reviewed by, for example, Solanki et al., BioMed Res. Int. 2013, Article ID 620719), or any other form preserving the activity and/or viability of the bacterial strain.

The composition as taught herein may be a pharmaceutical composition. The pharmaceutical composition may be for use as a supplement. A pharmaceutical composition will usually comprise a pharmaceutical carrier, in addition to the first bacterium and/or second bacterium taught herein. The carrier is preferably an inert carrier. The preferred form depends on the intended mode of administration and (therapeutic) application. A pharmaceutical carrier can be any compatible, nontoxic substance suitable to deliver the bacterium taught herein to the GI tract of a subject. For example, sterile water or inert solids may be used as a carrier, usually complemented with a pharmaceutically acceptable adjuvant, buffering agent, dispersing agent, and the like. A pharmaceutical composition as taught herein may be in liquid form, e.g. a stabilized suspension of bacteria of the bacterium taught herein, or in solid form, e.g., a powder of lyophilized bacteria taught herein. In case the bacterium taught herein is lyophilized, a cryoprotectant such as lactose, trehalose or glycogen can be employed. E.g., for oral administration, the first bacterium and/or second bacterium taught herein can be administered in (separate) solid dosage forms, such as capsules, tablets, and powders, comprising lyophilized bacteria, or in (separate) liquid dosage forms, such as elixirs, syrups, and suspensions. The first bacterium and/or second bacterium taught herein, e.g., in lyophilized form, can be encapsulated in capsules such as gelatin capsules, together with inactive ingredients and powdered carriers, such as e.g. glucose, lactose, sucrose, mannitol, starch, cellulose or cellulose derivatives, magnesium stearate, stearic acid, sodium saccharin, talcum, magnesium carbonate and the like.

In an embodiment, the first bacterium and/or second bacterium as taught herein may be comprised in the composition as taught herein in an amount ranging from about 10° to about 10" colony forming units (CFU). For instance, the intestinal bacteria may be comprised in the composition in an amount of about 107 CFU to about 10 CFU, preferably about 108 CFU to about 103 CFU, more preferably about 10° CFU to about 102 CFU, even more preferably about 1012 CFU to about 10%2 CFU, e.g. for each of the first bacterium and/or second bacterium.

The present disclosure also provides for a composition obtainable by:

a) growing the first bacterium as taught herein and optionally a second bacterium as taught herein in an aqueous medium suitable therefor (the aqueous medium may comprise phytate); b) after step a), separating the first bacterium and optionally the second bacterium from the aqueous medium to thereby obtain the composition (i.e. the aqueous medium separated from the first bacterium and optionally the second bacterium). The composition may comprise (3-hydroxy)propionate.

In the present disclosure, it is preferred that the first bacterium and/or second bacterium, or composition taught herein, is not comprised in fecal matter. In this regard, the term ‘fecal matter includes feces or a fraction thereof, such as obtained by mixing feces with aqueous medium and subsequent filtering and/or centrifugation.

Methods and uses

The present disclosure is concerned with a first bacterium and/or second bacterium as taught herein or a composition as taught herein for use as a medicament, for use as a food or food supplement, or for use as a probiotic and/or symbiotic.

In a preferred embodiment, the first bacterium and/or second bacterium for use according to the present disclosure may be administered separately, sequentially or simultaneously with phytate or with a phytate source, which may be present in the same composition as the first bacterium and/or second bacterium, or in a separate composition, for example, comprising in the range of from about 5 mM to about 100 mM, preferably from about 10 mM to about 50 mM, more preferably from about 15 mM to about 25 mM, and even more preferably about 20 mM phytate, or for example comprising from about 1 mg to about 1000 mg, preferably from about 10 mg to about 500 mg, more preferably from about 15 mg to about 50 mg.

Alternatively, the amount of phytate and/or administration frequency may be chosen such that between 0.1 g and 100 grams is consumed per day, for example between 0.5 g and 10 g per day or between 0.1 g and 5 g per day.

The present disclosure particularly pertains to the first bacterium and/or second bacterium as taught herein or (separate) composition comprising the same as taught herein for use in maintaining, restoring and/or improving Gl health in general, and/or for preventing and/or treating conditions or diseases such as obesity, metabolic diseases, such as metabolic syndrome and insulin resistance or insulin resistance-related complications, such as (metabolic) Adenylosuccinate lyase deficiency ((M)ASLD) / (metabolic) dysfunction- associated steatohepatitis ((M)ASH), dyslipidemia and type 2 diabetes mellitus as well as insulin-resistance in endocrine diseases (e.g., obese subjects with type 1 diabetes mellitus,

Cushing's disease or lipodystrophy syndromes). In addition, foreseen is use for not gaining weight, such as after having lost weight e.g. following GLP1 agonist therapy. Furthermore, foreseen is use for maintaining weight {within 1, 2, 3, 4 or 5% margin with respect to said weight), such as during and/or after GLP1 agonist therapy. Without being bound by theory, the first and/or second bacterium according to the present disclosure (optionally administered together with phytate) may have satiety effects since in situ propionate is provided (see Int.

Dairy J. 18, 945-950 (2008)).

The present disclosure is also directed to a method for maintaining, restoring and/or improving Gl health in general, and/or for preventing and/or treating conditions or diseases such as obesity (i.e. a body mass index (BMI) over 25, 26, 27, 28, 29, preferably over 30), metabolic diseases, such as metabolic syndrome and insulin resistance or insulin resistance-related complications, such as dyslipidemia and type 2 diabetes mellitus as well as insulin-resistance in endocrine diseases {e.g., obese subjects with type 1 diabetes mellitus,

Cushing's disease or lipodystrophy syndromes) in a subject in need thereof, said method comprising the step of increasing the level of the first bacterium and/or second bacterium as taught herein in said subject. It has also been found that the present disclosure, e.g. the first bacterium and/or second bacterium as taught herein, may be for use in enhancing (intestinal) epithelial barrier function. In this regard, see also Int. Dairy J. 18, 945-950 (2008); and Gut 2015;84:1744-1754. doi:10.1136/gutjnl-2014-307913. It has additionally been found that the present disclosure, e.g. the first bacterium and/or second bacterium as taught herein, may be for use in preventing or treating inflammatory disorders, such as rheumatoid arthritis, or inflammatory bowel disease. It has additionally been found that the present disclosure, e.g. the first bacterium and/or second bacterium as taught herein, may be for use in preventing or treating cancer such as colon cancer. The present disclosure also foresees use for enhancing satiety in a subject. The present disclosure shows in particular the increased propionate production in the gut that will increase satiety and as a consequence will reduce food intake and prevent weight gain (see Ruijschop et al. 2008 Chambers et al 2015).

The level of the first bacterium and/or second bacterium as taught herein in said subject may be increased by administering an effective amount of said first bacterium and/or second bacterium to said subject, and/or by administering an effective amount of a compound capable of increasing the level of said first bacterium and/or second bacterium in (the GI tract of) said subject.

In an embodiment, the first bacterium and/or second bacterium as taught herein may be administered concomitant with phytate or a phytate source, such as fruits, beans, grains, and nuts. The skilled person can, without undue burden, readily identify phytate-rich sources. In addition or alternatively, the first bacterium and/or second bacterium as taught herein may be administered to a subject following a diet which includes phytate, such as a subject following a vegetarian diet, vegan diet, or Mediterranean diet.

In a preferred embodiment, the level of the first bacterium and/or second bacterium as taught herein in the GI tract of a subject may be increased by administering to the subject an effective amount of the first bacterium and/or second bacterium as taught herein, preferably

Mitsuokella jalaludinii or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:93 and/or Anaerostipes rhamnosivorans 1y2 or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID

NO:94 and/or a composition as taught herein comprising said.

In an embodiment, the subject may be selected from the group consisting of human beings, (monogastric) animals such as non-human primates, mice, rats, cats, dogs, cows, and pigs. In a preferred embodiment, the subject is a human.

The disclosure also relates to a method for producing 3-hydroxypropionate and/or propionate, comprising the step of contacting the first bacterium and/or second bacterium as taught herein with a suitable energy source, e.g. phytate and/or glucose/acetate, under conditions which allow the first bacterium and/or second bacterium as taught herein to convert the energy source to 3-hydroxypropionate and/or propionate.

The methods taught herein may be in vitro methods.

GENERAL DEFINITIONS

The terms ‘probiotics’ and ‘probiotic products’ as used herein refer to microorganisms such as intestinal bacteria, which - when administered or ingested in effective amounts - confer health benefits to the host (e.g. mammals, such as humans). Preferably, probiotics should be alive or viable when administered to a subject so as to allow the probiotics to colonize the large intestine of the host. However, under certain conditions, probiotics may also be dead when administered provided that substances produced by the probiotics still exert probiotic, beneficial effects on the host.

The terms ‘prebiotics’ and ‘prebiotic products’ as used herein generally refer to compounds that promote the growth and/or activity of GI microorganisms that contribute to the well-being of their host. Prebiotics or prebiotic products consist mainly of fermentable fibres or non- digestible carbohydrates. The fermentation of these fibres by prebiotics promotes the production of beneficial end products, such as SCFAs, particularly butyrate. The skilled person is well-acquainted with the field of prebiotics and knows how to select ingredients endowed with prebiotic activity.

The terms ‘symbiotics’ and ‘symbiotic products’ as used herein generally refer to compositions and/or nutritional supplements combining probiotics and one or more compounds that promote the growth and/or activity of GI microorganisms, such as prebiotics, into one product. The symbiotic beneficially affects the host by improving the survival and colonization of the probiotic in the GI tract, by selectively stimulating the growth and/or by activating the metabolism of the probiotic, thus improving host welfare. The skilled person is well-acquainted with symbiotics and knows how to select ingredients that may be combined into a symbiotic.

The terms ‘propionate’ and ‘propionic acid’ as used herein refer to a carboxylic acid with chemical formula GH:CH2CQ:H. The terms may include derivatives thereof, i.e. compounds derived from propionic acid and in particular salts of propionic acid (propionates) and esters of propionic acid { propanoates). Propionic acid can be seen as a short-chain saturated fatty acid comprising ethane attached to the carbon of a carboxy group. Non-limiting examples of propionates are ammonium. propionate, calcium propionate, magnesium propionate, potassium propionate and sodium propionate. A non-limiting example of a propanoate is ethyl propionate.

The term ‘beneficial intestinal bacteria species’ as used herein refers to a bacterium species that inhabits (i.e. is innate) the mammalian (e.g. human) intestine and exerts beneficial effect(s) (e.g. protection against pathogenic bacteria species, production of butyric acid and/or butyrate and derivatives, etc.) on the Gl, metabolic and other health of a mammal in which it resides. Non-limiting examples of beneficial intestinal bacterial species include lactic acid bacteria from the genera Lactobacillus and Bifidobacterium. Other non-limiting examples of beneficial intestinal bacterial species include butyrate-producing bacterial species, which use the acetyl-CoA to produce butyric acid and/or butyrate and derivative thereof, such as the bacterial strains disclosed in US 2014/0242654, WO 2014/150094 or

WO 2013/032328.

The term ‘effective amount as used herein refers to an amount necessary to achieve an effect as taught herein. For instance, an effective amount of the first bacterium and/or second bacterium as taught herein is an amount which is effectively useful for maintaining, restoring, and/or improving GI heath in a human being, for converting phytate into 3- hydroxypropionate/propionate or a derivative thereof and/or for preventing and/or treating conditions or diseases described herein in a subject, preferably a human being. These conditions or diseases include, without limitation, obesity, metabolic diseases, such as metabolic syndrome and insulin resistance or insulin resistance-related complications, such as dyslipidemia and type 2 diabetes mellitus as well as insulin-resistance in endocrine diseases (e.g., obese subjects with type 1 diabetes mellitus, Cushing's disease or lipodystrophy syndromes). The effective amount can be readily determined without undue experimentation by a person of ordinary skill in the art.

The term ‘a strain that derives therefrom’ as used herein relates to strains obtained by using the deposited strain as taught herein as starting material. The strain that derives therefrom may be a mutant strain, which may be derived from a strain of the invention by means of, for instance, genetic engineering, radiation, UV light, chemical treatment.

Alternatively, such derivative or mutant strain may be a strain derived from the deposited strain as taught herein that has been subjected to growth adaptation to particular conditions resulting in an additional benefit to the derivative strain, such as more rapid growth, better survival in the gut, enhanced phytate to propionate conversion, using methods that are well- known to the skilled person. It is preferred that the derivative or mutant is functionally equivalent to the deposited strain as taught herein. A preferred derivative or mutant as taught herein has substantially the same activity or function as the deposited strain as taught herein, i.e. has the ability to convert phytate to 3-hydroxypropionate/propionate and derivatives. The derivative or mutant advantageously provides substantially the same benefits to a mammal (e.g. humans or other mammals) administered with said derivative or mutant as would be the case upon administration of the deposited strain. The derivative or mutant strain may also be a spontaneous derivative or mutant strain having the same characteristics as described herein for the deposited strain.

The term “isolated” may refer to being separated from its natural environment (which may be the gut or feces for example).

The terms ‘suitable for consumption’ and ‘nutritionally acceptable’ refer to ingredients or substances, which are generally regarded as safe for human (as well as other mammals) consumption.

The term ‘metabolic syndrome’ is well known by the skilled person. Within the present disclosure, the term encompasses all conditions diagnosed as “metabolic syndrome” by an (authorized) medical practitioner. For example, metabolic syndrome may be diagnosed if a patient has at least two or at least three of the following traits: - Large waist — A waistline that measures at least 35 inches (89 centimeters) for women and 40 inches (102 centimeters) for men; - High triglyceride level — 150 milligrams per deciliter (mg/dL), or 1.7 millimoles per liter (mmol/L), or higher of this type of fat found in blood; - Reduced "good" or HDL cholesterol — Less than 40 mg/dL (1.04 mmol/L) in men or less than 50 mg/dL (1.3 mmol/L) in women of high-density lipoprotein (HDL) cholesterol; - Increased blood pressure — 130/85 millimeters of mercury (mm Hg) or higher; - Elevated fasting blood sugar — 100 mg/dL (5.6 mmol/L) or higher.

The term ‘insulin resistance’ is well known by the skilled person. Within the present disclosure, the term encompasses all conditions diagnosed as “insulin resistance“ by an (authorized) medical practitioner. For example, insulin resistance may be diagnosed by the gold standard for determining and quantifying insulin resistance which is the "hyperinsulinemic euglycemic clamp" (DeFronzo RA, Tobin JD, Andres R (1979). The

American Journal of Physiology. 237 (3): E214-23). This method measures the amount of glucose necessary to compensate for an increased insulin level without causing hypoglycemia. The procedure may take about two hours and typically involves the following steps. Through a peripheral vein, insulin is infused at 10-120 ml) per m? per minute. In order to compensate for the insulin infusion, glucose 28% is infused to maintain blood sugar levels between 5 mmol/l. and 5.5 mmol/L. The rate of glucose infusion is determined by checking the blood sugar levels every five to ten minutes (Munivappa R, Lee S, Chen H, Guon MJ {January 2008}. American Journal of Physiology. Endocrinology and Metabolism. 294 (1): £1528). The rate of glucose infusion during the last thirty minutes of the test determines insulin sensitivity. If high levels (7.5 mg/min or higher) are required, the patient is insulin- sensitive. Low levels (4.0 mg/min or lower) indicate insulin resistance. Levels between 4.0 mg/min and 7.5 mg/min are not definitive and suggest "impaired glucose tolerance”, an early sign of insulin resistance. Alternatively, the homeostatic model assessment (HOMA) is a method used to determine and quantify insulin resistance, as it correlates reasonably with the golden standard, See e.g. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF,

Turner RO {1985}. Diabetologia. 28 17}: 412-8. doi:10.1007/BF00280883. PMID 3899825; andor A. S. Rudenski; D. RK. Matthews; J.C. Levy; R.C. Turner (1991) Metabolism. 40 (9): 408-917. A HOMA(-IR) score that deviates from a reference range can indicate insulin resistance. Alternatively, a fasting serum insulin level greater than 25 mU/L or 174 pmol/l. can be considered as indicating insulin resistance. The term “insulin resistance” as used herein refers to peripheral insulin resistance and/or hepatic insulin resistance. The term ‘insulin resistance-related conditions’ (or complications) may refer to dyslipidemia. Alternatively or additionally, the term may refer to type 2 diabetes mellitus. Further, the term ‘insulin resistance-related conditions’ (or complications) may refer to insulin-resistance in endocrine disease {e.g. ‚obese subjects with type 1 diabetes mellitus, Cushing's disease or lipodystrophy syndromes).

As used herein, the term “identity” refers to a measure of the identity of nucleotide sequences or amino acid sequences. In general, the sequences are aligned so that the highest order match is obtained. "Identity" per se has an art-recognized meaning and can be calculated using published techniques. See, e.g.: (COMPUTATIONAL MOLECULAR

BIOLOGY, Lesk, A. M., ed., Oxford University Press, New York, 1988; BIOCOMPUTING:

INFORMATICS AND GENOME PROJECTS, Smith, D. W., ed., Academic Press, New York, 1993; COMPUTER ANALYSIS OF SEQUENCE DATA, PART |, Griffin, A. M., and Griffin, H.

G., eds., Humana Press, New Jersey, 1994; SEQUENCE ANALYSIS IN MOLECULAR

BIOLOGY, von Heinje, G., Academic Press, 1987; and SEQUENCE ANALYSIS PRIMER;

Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991). While there exist a number of methods to measure identity between two polynucleotide or polypeptide sequences, the term "identity" is well known to skilled artisans (Carillo, H., and Lipton, D.,

SIAM J. Applied Math (1988) 48:1073). Methods commonly employed to determine identity or similarity between two sequences include, but are not limited to, those disclosed in GUIDE

TO HUGE COMPUTERS, Martin J. Bishop, ed., Academic Press, San Diego, 1994, and

Carillo, H., and Lipton, D., SIAM J. Applied Math (1988) 48:1073. Methods to determine identity and similarity are codified in computer programs. For example NCBI Nucleotide Blast with standard settings (blastn, https://blast.ncbi.nlm.nih.gov/). Preferred computer program methods to determine identity and similarity between two sequences include, but are not limited to, GCS program package (Devereux, J., et al., Nucleic Acids Research (1984) 12(1):387), BLASTP, BLASTN, FASTA (Atschul, S. F. et al., J. Molec. Biol. (1990) 215:403).

As an illustration, by a nucleotide sequence or amino acid sequence having at least, for example, 95% "identity" to a reference sequence, it is intended that the nucleotide sequence or amino acid sequence is identical to the reference sequence except that there may be up to five-point mutations per each 100 nucleotides or amino acids of the reference sequence. In other words, to obtain a nucleotide sequence or amino acid sequence being at least 95% identical to a reference sequence, up to 5% of the nucleotides or amino acids in the reference sequence may be deleted and/or substituted with another nucleotide or amino acid, and/or a number of nucleotides or amino acids up to 5% of the total nucleotides or amino acids in the reference sequence may be inserted into the reference sequence. Preferably, the sequence identity refers to the sequence identity over the entire length of the sequence. It is further understood that, when referring to “sequences” herein, generally the actual physical molecules with a certain sequence of subunits (e.g. amino acids or nucleotides) are referred to.

The term ‘about as used herein indicates a range of normal tolerance in the art, for example within 2 standard deviations of the mean. The term ‘about’ can be understood as encompassing values that deviate at most 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the indicated value.

The terms ‘comprising’ and ‘to comprise’ and their conjugations, as used herein, refer to a situation wherein said terms are used in their non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. It also encompasses the more limiting verb ‘to consist essentially of and ‘to consist of.

Reference to an element by the indefinite article ’a’ or ‘an’ does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there be one and only one of the elements. The indefinite article ‘a’ or ‘an’ thus usually means ‘at least one’.

The terms ‘to increase’ and ‘increased level’ and the terms ‘to decrease’ and ‘decreased level refer to the ability to significantly increase or significantly decrease or to a significantly increased level or significantly decreased level. Generally, a level is increased or decreased when it is at least 5%, such as 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% higher or lower, respectively, than the corresponding level in a control or reference. Alternatively, a level in a sample may be increased or decreased when it is statistically significantly increased or decreased compared to a level in a control or reference.

Description of the figures

Figure 1: Fecal phytate metabolism and identification of phytate-degrading Mitsuokella spp. a: 13C-NMR spectra of ['3Cs]InsPs metabolism by fecal microbiome of donor A during 24h incubation. Dashed lines connect NMR signals of identified metabolites and CO... For 3-hydroxypropionate dotted lines are used for better visibility. The final metabolic products derived from [**Ce]InsPs are [*C;lacetate, ['*Cs]propionate, and [13C4]butyrate. [*C3]3-hydroxypropionate accumulates transiently between 4.5 - 6.5 h. b: Microbial composition of fecal samples, the initial time points and end time points of phytate enrichment from donor A. Top 15 abundant taxonomic groups in the samples are shown in colors and the rest is shown as other in white. ¢: Changes of relative abundance of Mitsuokella jalaludinii and Mitsuokella spp. during phytate incubation and phytate consumption in fecal enrichments from donor A.

Figure 2: Elucidation of phytate degradation pathway in Mitsuokella jalaludinii

DSM13811'. a: Faster growth of M. jalaludinii in 10mM and 40mM phytate as compared to growth in 10mM and 40mM myo-inositol while similar metabolite production was observed. b: C-NMR analysis shows rapid ['3Cs]phytate degradation with ['3Cs]Ins(2)P and [’3Cs]Inositol as intermediates and [?C:]3-hydroxypropionate, ['*Cs]lactate, [13Cs]succinate, and ['3Cz]acetate as end metabolites. ¢: BIRD-{'H,"*C}HMQC spectrum of the M. jalaludinii culture sample at 7.5 h. The region in which inositol polyphosphate signals are commonly found is shown. The mixture contains the starting material [**Cs]InsPs (purple arrows) but also the dephosphorylation products Ins(2)P (blue arrows) and myo-inositol (grey arrows). Each detectable signal is annotated with the corresponding substance name and position of the inositol ring. Note that each of the detected substances exhibit four NMR signals each due to the Cs-symmetry of the six-membered inositol ring, and therefore, positions C1 and C3 are magnetically equivalent and so are positions C4 and C6. d: Log2fold change of differential expression of genes involved in phytate degradation; inositol and phosphate uptake and inositol metabolic genes comparing between phytate and inositol condition (Table S2).

Predicted functional groups of these genes are indicated on the right. e: Reconstruction of the entire phytate degradation pathway based on genomic, transcriptomic and metabolomic analyses. The genes have been identified a genome from GenBank (BioProject

PRJNA223472) of M. jalaludinii DSM138117 and re-annotating the genome in Rapid

Annotation using Subsystem Technology (RAST).

Figure 3: Mechanistic insight into the synergy between M. jalaludinii and

A. rhamnosivorans in phytate degradation. a-b: Metabolite production and substrate consumption by monoculture of M. jalaludinii (a) and coculture of M. jalaludinii and

A. rhamnosivorans (b) in phytate (n=2 biological replicates). Data are presented as mean valuestSD. c: ®*C-NMR spectra of [**Ce]InsPs metabolism by coculture of M. jalaludinii and

A. rhamnosivorans during 48 h incubation. Dashed lines connect NMR signals of identified metabolites and CO:. Dotted lines are used for 3-hydroxypropionate to provide better visibility.

The final metabolic products derived from [**Ce]InsPs are [*C.]acetate, ['*Cs]propionate, ['3Cs]lactate, [13C3]3-hydroxypropionate, [3C]butyrate, and [**C4]succinate. [*C4]succinate is again formed as a mixture with partially or non-**C-labeled succinate. The same InsP intermediates can be observed between 2 - 7.5 h as for the monoculture (Fig. 3b). d: M. jalaludinii (MJ): Log2fold change of differential expression of genes involved in phytate degradation; inositol and phosphate uptake and inositol metabolic genes comparing between monoculture and coculture. Functions of these genes are indicated on the right. e: A. rhamnosivorans: Log2fold change of differential expression of genes involved in inositol uptake, inositol metabolic genes, propionate production and 3-hydroxypropionate transport comparing between MA_I (coculture in myo-inositol) versus A_l (monoculture in myo-inositol);

MA_P (coculture in phytate) versus A_I (monoculture in myo-inositol }; MA_P (coculture in phytate) versus MA_I (coculture in myo-inositol}. Predicted functional groups of these genes are indicated on the right. The transcriptomic analysis was performed in biological triplicate. f: Reconstruction of synergistic interaction between M. jalaludinii and A. rhamnosivorans in phyate. M. jalaludinii uses periplasmic phytase to dephosphorylate phytate rapidly to Ins(2)P and inositol, which can subsequently be taken up and be used to produce succinate, acetate, lactate and 3-hydroxypropionate. The produced 3-hydroxypropionate is released into the medium and inhibits myo-inositol uptake by A. rhamnosivorans. A. rhamnosivorans, in turn, metabolizes 3-hydroxypropionate via a 3-hydroxypropionate scavenging pathway to produce propionate, conserving energy by coupling the electrochemical gradient generated via a membrane bound Rnf complex with ATP synthesis.

Figure 4: In vivo phytate conversion by M. jalaludinii and A. rhamnosivorans in mice. a: experimental design of in vivo microbial phytate conversion. Three groups of 8 mice were treated with either phytate (0.1mg/g body weight) alone, or phytate (0.1mg/g body weight) together with M. jalaludinii (109 cells per dose) or phytate (0.1mg/g body weight) with

M. jalaludini (MJ) and A. rhamnosivorans (A.rham) (1049 cells per strain per dose) every second day for two weeks. After two weeks, a ['*Cs]phytate oral challenge of the same bacterial dosage were performed for the respective group. A group of four mice was sacrificed after 3 h or 6 h. Cecum and plasma samples were harvested for inositol phosphate extraction and measurement while colon samples were used far quantification of M. jalaludinii and A. rhamnosivorans via QPCR. Significant lower levels of cecal ['*Cg] phytate in microbial treatment groups compared to control groups at 3 h (b) and 6 h (c) after oral challenge.

Relative abundance of Mitsuokella jalaludinii at 6 h {d) and A. rhamnosivorans at 8 h (e) in murine colon samples quantified via qPCR in three groups: Phytate (purple);

Phytate_A.rham_MJ (blue) and phytate_MJ (orange). Quantification of three ['*Cs¢]InsPs species: InsPs[30OH] at 6 h (f), Ins(1,2,5,8)P4 at 8 h (g); InsP:[5OH] at 3 h (h) in the cecum samples by BIRD-{'H,"*C}HMQC spectra at 6 h and 3 h after oral challenge. Relative abundance of A. rhamnosivorans (g) and Mitsuokella jalaludinii (h) in colon samples quantified via qPCR in three groups: Phytate (purple); Phytate_A.rham_MJ (blue) and phytate_MJ (orange). i: Postulated phytate degradation routes in mouse cecum. Black arrows indicate the route involved Mitsuokelia jalaludinii and A. rhamnosivorans while grey arrows are routes by the mouse microbiome alone. Two arrows indicate conversion required more than one reaction. Shown values are means + SEM (n=4) and statistical analysis was performed using one-way ANOVA. Only significantly different comparisons are shown. *P<0.05; **Ps0.01; ***Ps0.001.

Figure 5: Propionate and phytate-derived bacterial metabolites improved epithelial barrier integrity via activating tight junction genes. a: 20mM propionate co-incubation increased TEER values as compared to the control. b: Increased activity of tight junction genes Claudin-1, Claudin-2 and E-cadherin upon propionate exposure. Increased barrier integrity when Caco-2 cells were incubated with 10% bacterial supernatant from a coculture (M. jalaludinii and A.rhamnosivorans) compared to 10% the medium control. d: Increased activity of tight junction genes Claudin-1 and E-cadherin upon bacterial supernatant exposure compared to the medium control. Shown values are means + SD (n=4 biological replicates) and statistical analysis was performed by two-way ANOVA. Only significantly different comparisons are shown. *P<0.05; **P<0.01,; ***P<0.001; ****P=<0.0001.

Figure 6: Concentration independent synergy between M. jalajudinii and A. rhamnosivorans for phytate breakdown. a: Growth curves of co-cultures (blue) of

M. jalajudinii and A. rhamnosivorans and monocultures (pink) of M. jalajudinii in 10 mM, 20 mM, and 40 mM phytate during 24 h incubation. b: End metabolite production of the co-cultures and monocultures of cocultures (blue) of M. jalajudinii and A. rhamnosivorans and monocultures (pink) of M. jalajudinii in 10 mM, 20 mM, and 40 mM phytate after 24 h incubation. Shown values are means + SD (n=3).

Figure 7: 3-hydroxypropionate metabolism by A. rhamnosivorans. A. rhamnosivorans was found to co-metabolize 3-hydroxypropionate. Fermentation profiles are shown of

A. rhamnosivorans incubated in glucose (a) (a); glucose and 3-hydroxypropionate {b); 3-hydroxypropionate (¢) and myo-inositol plus 3-hydroxypropionate (HP) (d) by

Anaerostipes rhamnosivorans. All experiment were performed in biological duplicate. Shown values are means + SD (n=2).

Figure 8: Transcriptome analysis reveals synergy study M. jalaludinii and

A. rhamnosivorans. Metabolite production and substrate consumption of phytate (a) and myo-inositol (b) by monocultures and co-cultures of M. jalaludinii and A. rhamnosivorans. Cell numbers of M. jalaludinii and A. rhamnosivorans quantified by qPCR in the coculture on myo-inositol (¢) and phytate (d). e: Principal coordination plot of the transcriptional profiles obtained by RNA-seq of M. jalaludinii when grown on phytate {(green/purple) or myo-inositol (red/blue) in the presence (blue/purple) or absence (red/green) of A. rhamnosivorans (Table

S2-7). Ordination was based on centered log transformed counts and Euclidean distance.

The experiment was performed in biological triplicate. Shown values are means + SD (n=3).

Figure 9: Reconstruction of 3-hydroxypropionate conversion to propionate by

A.rhamnosivorans. 3-hydroxypropionate is imported via a permease (AR1Y2_1114) and further converted to 3-hydroxy propionyl-CoA, Acryloyl_CoA, propionyl-CoA and eventually propionate via oxoacid CoA transferase (AR1Y2_1115), dehydratase (AR1Y2_1116), acad-etf complex (AR1Y2_1112, 1113 and 1117). Acyl-CoA dehydrogenase/Etf complex (AR1Y2_1112, 1113 and 1117} is predicted to be involved in energy conservation via by coupling the electrochemical gradient generated via a membrane bound Rnf complex with

ATP synthesis.

Figure 10: Enrichment of 13C-short chain fatty acids in mouse ceca upon bacterial oral challenge. Relative abundance of one 13C (m1); two *C (m2); three 3C (m3) and four 13C (m4) of 13C-propionate (a); 13C-butyrate (b) and 13C-acetate (c) in mouse cecum in three treatment groups: Phytate (brown); Phytate_A.rham_MJ (blue) and phytate_MJ (green).

Shown values are means + SD (n=4 except Phytate_MJ at 3h (n=2) and Phytate_A.rham_MJ and Phytate_MJ at 6h (n=3) due to technical issues during derivatization).

Figure 11: Production of bacterial supernatant of the co-culture for epithelial barrier function test using a Caco-2 cell model. The experiment was performed in YCFA medium supplemented with phytate. Around 20 mM phytate was repeatedly added after adjusting the pH to neutral (~7). Bacterial supernatants was collected before and after substrate addition for 5 days. In the end of the growth, propionate, acetate and succinate were found as major end metabolites with nearly 90 mM propionate. Red arrows indicate the time of phytate addition.

Sequence listing ttgctttatcatatcctgcacaaaaaaataaatttctctetgetgetggecgtetgtctgatactaataaatgcaccagcecategetge ggctgcagttcctgaggaacctgcctggcggctcgatgcggccatcggcagtgacgagccgattcatttccgccgcgatgcag atcttaaaatcgcgggcggcgggcagccgacaaaagaagtcctegcccatctgcccgcacttetcggegtcccgcccgatat gcctatctgggatattgacctgcggcaggaatcccacggctttctcaatcatgcggccgtgagctggcatggcccgcagaatgc ggcgaatcgcggccttgccgcaacagaagtcgaacaagacgaaacggcccgcctgcaggaggcccttggacaccttgtcc aagccctgccgatgggccgctacgatgaagaacatatcaaaacatcttttgctgaaccagtagagagctggtcaacggaacg cgaactggcgcgcagagccgggctcggctacaagcgctttgecgcgaccgatatggaatggccggggcctgcggtcatcga tgacttcgtcgacttttaccgcagcctgccaaagaatcacggctggctcttcttccactgccaggccggacagggccgtacgac gacgtttatggtactctatgagctgctggaacatccatccgtcaccgcagatgaggcaattgcgcatcagcgcagcctaggcgg tgccgacctttcaagcgggccgcgttatcatggcctgcagcttttcgcccattatgtcaaagaaaactgtgcgtcaaattttcagca aacatggagccagtggctggctgcccgacaaaattcttactaa

Amino acid sequence (SEQ ID NO:2)

MLYHILHKKINFSLLLAVCLILINAPAIAAAAVPEEPAWRLDAAIGSDEPIHFRRDADLKIAGG

GQPTKEVLAHLPALLGVPPDMPIWDIDLRQESHGFLNHAAVSWHGPQNAANRGLAATEV

EQDETARLQEALGHLVQALPMGRYDEEHIKTSFAEPVESWSTERELARRAGLGYKRFAAT

DMEWPGPAVIDDFVDFYRSLPKNHGWLFFHCQAGQGRTTTFMVLYELLEHPSVTADEAIA

HQRSLGGADLSSGPRYHGLQLFAHYVKENCASNFQQTWSQWLAARQNSY

Nucleotide sequence (SEQ ID NO:3) atggcggaatcatctcatcgcaaatacctcaagcgtgtcacagtcgtctcgacgtteggtggcttgctcttcggttatgacaccgg cgtcatcaacggcgcccttgccttcatggcccgtccggatcagttgaacctgactccggcagtggagggcttcgtggccagtgg cctgctcttcggtgcggccatcggttegttettcggcggccgtctttcggatgctgagggacgccgcaagatgctgctttgcctggc agtcatcttcttcttcgcagccatcggetgctegctgtcaccgacggctggcatcctcatcgcctgcegcttegtccteggcctggc agtcggtggtgcttcggtcacggtacctgcttacctggcagagatggcaccggccgacaggcgcggccgcatggtcacccag aatgagctcatgatcgtcacgggccagctgctcgccttcatcctcaacgctatcctcggcgtcaccttcggtgaggtcggccaca tctggcgttacatgctcgcactcgcatccatcccggctgtcgtgctctggttcggcatgctcgtgatgccggagagcccgcgctgg ctgctgctgcagggccgtgtcagcgatgcgatgcaggtactcaagaagatccgcgatgagcgcatggccatcgccgagctca acgagatccaggacagcatcgattcggagaagcatctcgacaaggctggttacaaggacctggcaacgccttggatccgcc gcatcgtcttcatcggcatgggcgtctccatctgccagcagatttctggcgtcaactccatcatgtattacggcacgcagatcttga cgcaggccggcttctcgacggaagccgcactgatcggcaacatcgccaacggcacgatctccgttgetgccacaatctttggc atgtggctcatgacgcgtcacggccgtcgtccgctcatcatgacgggccagatcggcacgatggcctgcctctgcgcgatcgg cgttctctcgaatctgcttgccggcaccgagatcctgccgttcgtcgtcctttegetgaccgtcaccttcctgttettccagcagggttt cctttccccggtcacctggctgctgctetcggagctcttcccgetgcgcatccgcggcatgggcatgggctgcgccgtcctctgcc tctggctgacgaacttctgcatcggctcggccttcccgtegetgctetactcgtteggcctetcggctacgttcttcatcttegcggcc atcggccttcteggcctcgccttcgtctacaagttcgtgccggagacgcgtggccgcacgctcgagcagatcgagcatgacttc cgccatcacggtgagaagagcgttcactgcgaagagaaagcttga

Amino acid sequence (SEQ ID NO:4)

MAESSHRKYLKRVTVVSTFGGLLFGYDTGVINGALAFMARPDQLNLTPAVEGFVASGLLF

GAAIGSFFGGRLSDAEGRRKMLLCLAVIFFFAAIGCSLSPTAGILIACRFVLGLAVGGASVTV

PAYLAEMAPADRRGRMVTQNELMIVTGQLLAFILNAILGVTFGEVGHIWRYMLALASIPAVV

LWFGMLVMPESPRWLLLQGRVSDAMQVLKKIRDERMAIAELNEIQDSIDSEKHLDKAGYK

DLATPWIRRIVFIGMGVSICQQISGVNSIMYYGTQILTQAGFSTEAALIGNIANGTISVAATIF

GMWLMTRHGRRPLIMTGQIGTMACLCAIGVLSNLLAGTEILPFVVLSLTVTFLFFQQGFLSP

VTWLLLSELFPLRIRGMGMGCAVLCLWLTNFCIGSAFPSLLYSFGLSATFFIFAAIGLLGLAF

VYKFVPETRGRTLEQIEHDFRHHGEKSVHCEEKA atgattaaagttggtattatcggtgcaggccgtatcggtcatgtacatggcgagagcatctcgaagttcgtcaagaacgcaacg gtcaagacgattgctgatccgttcatgaacgagaagacggaagcttgggcaaagtccctcggcatcgagaagacgacgaaa gattaccatgagatcctcaacgatcctgaaattgaagccgtcctgatctgcgcttccacggaccagcattccccgctctccatcg aagcactgcgcgccggcaagcacgtcttctgtgagaaaccgattgaccatgatgtcaataagatcaaggaagttctcgacgtc gtcaaagagacgggcaagaaataccaggtcggcttcaaccgccgctttgaccacaacttcaaggctatccgcgatgctgtcgt cgccggaaaagtcggcaagcagcagatcatcaagatcacgtcccgtgatccggaaccgccttccatcgattacgtaaagattt ccggcggtatcttcctcgacatgacgattcatgatttcgatatggtccgctatctctccggcgcagaagtcgaggaagtatatgca gagggctctgtcaccgtcgatccggaaatcggcaaggctggcgacatcgatacggccatcatcacgctgaagctcgacaatg gcgctacggctgtcatcgacaactgccgtgccgcttgctatggctatgaccagcgcgctgaagtcttcggcacaaagggctgc gtcgccatctccaacgattcggattccaatgcagtctacagctgcaaggacggcgtcatcgccgagaagccgatgttcttctttct cgagcgctacatgatggcttatgcaaacgaagtcaatcagttcgtcgaagcgatcgtcaacgacacgccgaccccggtcaat gcaaacgacggcctgcagccggtcctcattggcctcgctgccaagaagtcggtcgaagagcatcgcccggtcaagattgca gagatccgcgcccagtacggcctctga

Amino acid sequence (SEQ ID NO:46)

MIKVGIIGAGRIGHVHGESISKFVKNATVKTIADPFMNEKTEAWAKSLGIEKTTKDYHEILND

PEIEAVLICASTDQHSPLSIEALRAGKHVFCEKPIDHDVNKIKEVLDVVKETGKKYQVGFNR

RFDHNFKAIRDAVVAGKVGKQQIIKITSRDPEPPSIDYVKISGGIFLDMTIHDFDMVRYLSGA

EVEEVYAEGSVTVDPEIGKAGDIDTAIITLKLDNGATAVIDNCRAACYGYDQRAEVFGTKGC

VAISNDSDSNAVYSCKDGVIAEKPMFFFLERYMMAYANEVNQFVEAIVNDTPTPVNANDG

LQPVLIGLAAKKSVEEHRPVKIAEIRAQYGL

Nucleotide sequence (SEQ ID NO:5) atggctaatatcaaacttggtatcgctccgattgcttggacgaacgacgacatgccggatctcggcaaagagaatacgtttgaa cagtgcgtcagtgagatggcactggctggcttcacgggctgcgagatcggcaacaagtacccgaaagatccggctgtcctca agaaagcactcgaccttcgcggactccagatcgccagcgcatggttcagctcctacctcctcacgcagccgtacgagcaggt cgagaaggacttcatcaagcactgcgaattcctcaaggccatgggcgcgaagttctgcaacgtcgcagagcagggcacga gcgttcagggcaagctcgacaaggctgtcttccgcgacaagccgcacaacacggaagagcagtggaagacgctcgctgag ggcctcaacaagctcggtgctgtcgccaagaagattggcctgacgatgacgtaccatcatcacatgggcacctgtgtccagac gacggaagagattgaccgcctcatggagatgacggatccagacctcgtcttcctgctctacgatacgggccatctcgtctgctc cggtgaggacccgatctacatcctcaagaagtacctgccgcgcatccgtcacgtacatctcaaggacatccgcatggacatcc gcaacaaagtcaaggaagagaacatgagcttccttgcaggcgtccgcgcaggcatgttcacggtcccgggcgatggcgact tcgacttcggtccggtcttcgacatcatcaatgacagcgactacgatggctggttcatcgtcgaagctgagcaggatccggcca aagccaacccgctcgagtacgcgatcaaagctcgcaagtacatcaaggaaaaagcacatatctga

Amino acid sequence (SEQ ID NO:6)

MANIKLGIAPIAWTNDDMPDLGKENTFEQCVSEMALAGFTGCEIGNKYPKDPAVLKKALDL

RGLQIASAWFSSYLLTQPYEQVEKDFIKHCEFLKAMGAKFCNVAEQGTSVQGKLDKAVFR

DKPHNTEEQWKTLAEGLNKLGAVAKKIGLTMTYHHHMGTCVQTTEEIDRLMEMTDPDLVF

LLYDTGHLVCSGEDPIYILKKYLPRIRHVHLKDIRMDIRNKVKEENMSFLAGVRAGMFTVPG

DGDFDFGPVFDIINDSDYDGWFIVEAEQDPAKANPLEYAIKARKYIKEKAHI

Nucleotide sequence (SEQ ID NO:7) atggctaagacaatcagactcacggtagcacaggctctcgtgaagttcctcaataatcagtatgtagaatttgacggcaagga agtgccgatgttcgaaggcatcttcggcatctteggccacggcaatgtcatcggcatcggccaggctctcgaagaggatccgg gccatctgatcatgcgcatgggccgcaatgagcagggcatggcacacgcagcgatgggctttgccaagcagaagcgccgc aagcagatgtacgcctgcacgtcttccgtcggcccgggcgctgccaacatggtcacggcagctgctacggctacggcaaact gcatcccagtcctgttcctgccgggtgacacgtacgccgaccgccagccggatccggtactccagcagatggagcagacggt aagcctgacgacgacgacgaacgacgcctticcgegcetgtetgcaaatactgggaccgegtcacgegtectgaaatectcatg acggcctgcatcaatgcgatgcgcgtcctgacggatccggctgagacgggtgctgtctgcatcgetctgccgcaggatgtcga aggcgaggcctgggattacccagattacttcttccagaagcgcgttcatcacatcgaccgcgtaaaaccgacggagcgcgcc attgaagaggctgtcaaggccatcgcgaaggctgagcgcccgctgatgatcttcggcggcggcgtcaagtattccgaggcag aggctgtcttccagaaattcgctgagaagtacggcatcccgttrggcgagacgcaggccggcaagggcacgattacgtggg agcatgagctcaacatgggcggcgtcggcgagacgggcggccttgcagccaacacgcttgcaaaagatgcagatgtcgtc atcggcgtcggcacgcgatacacggacttcacgacgtcctctaagtggatcttccagaacccgaacgtccagtacgtcaacat caacgtctcccgcttccatgcctacaagctcgatggcatccaggttgtcggcgatgccggcgcagcactcgagatgctcgatga ggccctcggcaagacgggctaccatgtgtcggatgcctatgctgcggacatcaaggcagccaaggaagcctatacgaagg aagtcgagcgtgtcttccacatccagttcggcgacaacttcgtgccggaagtcgacgatgatttcgattacaaggctgcagaga aagcctataaagaggcagtcggcgagacgctgccgcagacgcgcgtcctcggtctgctcgaagagcacatggatccgaac ggcatcatcgtcggtgcatcgggctccctgccgggcgacctgcagcgcgtatggcgtccgaagacggttggcagctaccatgt cgagtacggcttctcctgcatgggttatgaagtcaacgcagcactcggcgtcaagctcgctgagccgcagcgcgaagtctatg cgctcgttggcgactacgcttacatgatgctccattcggaactgccgacgtccatcgctgagggcaagaagatcaacgtcatcc tgttcgacaacatgcagggcggctgcatcaacaacctcgagatcggccatggccagggcagctacggcacggagttccgctt ccgcaacgagaagacgggccagctcgacggtgcctatgtaccggttgacttcgccatgaacgccgcttcctacggctgcaag agctacacggctcataccgaggaagagctcatcgcggccatcgaagatgctaagaagcagaaagtctcgacgctcatcgac tgcaaggtcatgccgaagacgatggttcacggctacggtgactggtggcgtgtcggcgtcgcgcaggtctccaagagcaaga agatccacgactgctacgagaatctcatgaagccgcattacgatgcagctcgcaagtattga

Amino acid sequence (SEQ ID NO:8)

MAKTIRLTVAQALVKFLNNQYVEFDGKEVPMFEGIFGIFGHGNVIGIGQALEEDPGHLIMRM

GRNEQGMAHAAMGFAKQKRRKQMYACTSSVGPGAANMVTAAATATANCIPVLFLPGDT

YADRQPDPVLQQMEQTVSLTTTTNDAFRAVCKYWDRVTRPEILMTACINAMRVLTDPAET

GAVCIALPQDVEGEAWDYPDYFFQKRVHHIDRVKPTERAIEEAVKAIAKAERPLMIFGGGV

KYSEAEAVFQKFAEKYGIPFGETQAGKGTITWEHELNMGGVGETGGLAANTLAKDADVVI

GVGTRYTDFTTSSKWIFQNPNVQYVNINVSRFHAYKLDGIQVVGDAGAALEMLDEALGKT

GYHVSDAYAADIKAAKEAYTKEVERVFHIQFGDNFVPEVDDDFDYKAAEKAYKEAVGETL

PQTRVLGLLEEHMDPNGIIVGASGSLPGDLQRVWRPKTVGSYHVEYGFSCMGYEVNAAL

GVKLAEPQREVYALVGDYAYMMLHSELPTSIAEGKKINVILFDNMQGGCINNLEIGHGQGS

YGTEFRFRNEKTGQLDGAYVPVDFAMNAASYGCKSYTAHTEEELIAAIEDAKKQKVSTLID

CKVMPKTMVHGYGDWWRVGVAQVSKSKKIHDCYENLMKPHYDAARKY

Nucleotide sequence (SEQ ID NQO:9) atgagattcggtcgcttaggtcagctcaagcacggctacaatgcaatgacgacgcgcgagagcgatatgctcatggatatcgg ttaccaggagatggatgagaacgagatcgtcgagttcgaagatccccttcaggagacggccttcgtcatcacgacgggtgatg tggagatctgctggaatggcaagaaagagctcatgcatcgcgagtcgctgctcgacgagaacccgtactgcctgcacgtgcc gcacggcgtcaaggtcgtcgtcaaggccctgaagaaatcggagctcctgatccagaagacgctcaacgaccgcgactttga gccggtcttctaccgtccgaaagatgtccaggctgacgttttcggcggcggcgtatggcagggcacggcagagcgcacggtc cgcacgatcttcgattacgacaatgcgccgtactccaacatggtcaacggcgaagtcatcatgacgccgggctgctggacgg gctacacgccgcacaatcatccgcagccggaagtctacacctacaaagtcgaccgtccgcagggctttggctgtgcgttcatc ggcgacaacgtcttcaagatcgaggacaacacttggtcggagatctcgggcggctacatgcatccgcagtgcgcagctcctg gctacgccatctggtacagctggatgattcgtcatctcgacggcgatccgtggaagaagacgcgcaatgacctgccggagca cacctggctgctcgagccggatgccgattcgaagatctggcagccgcacaagaagtga

Amino acid sequence (SEQ ID NO: 10)

MRFGRLGQLKHGYNAMTTRESDMLMDIGYQEMDENEIVEFEDPLQETAFVITTGDVEICW

NGKKELMHRESLLDENPYCLHVPHGVKVVVKALKKSELLIQKTLNDRDFEPVFYRPKDVQ

ADVFGGGVWQGTAERTVRTIFDYDNAPYSNMVNGEVIMTPGCWTGYTPHNHPQPEVYT

YKVDRPQGFGCAFIGDNVFKIEDNTWSEISGGYMHPQCAAPGYAIWYSWMIRHLDGDPW

Nucleotide sequence (SEQ ID NO: 11) atggcactcattagctttgatgaaaacaagaaacgcgatgtcgtcctgattggccgcgtcacgctggatttcaatccgaatgaac tgaaccgcacgctggacaaggtcaagactttctccatgtacctcggcggttcgccgggaaacatggctgtcggcatcaacaag ttgggcaagaacgtcggtttcatcggctgtgtatctgacgaccagttcggcgacttcgtcctcaattacttcaatgagcgtggcatt gacacgtcccagatgacgcgcgccaagaacggcgagcgcatgggtctgacgttcacggagatcaagagcccgacggagt cgagcatcctgatgtaccgcgaccaggtcgctgacctcgagattgcgccggaagatgtcgatgagcagtacatcgctgacag caagatcctgattgtctccggtacggcgctctcgaagagcccgtcgcgtgaggcatgcctgctggctgtccagtatgccaagaa acatggcacgcgcgtcatcttegatatcgactatcgcccgtacagctggcgcagcaagaaggacatccagatctactactcgtt gcttgcgagcatggccgatgtcatcatcggttcgcgcgatgaggtcaacctcacggaaggtctcgatgaggaggcaacggag ccggcagatcacgtcatcgctgagaagtacatcgagcagggtgccaagattgtcatcatcaagcacggcaagaagggctcg atcgcttacacggccgacaagaaggcctacaaggttgagtcgtaccacatcaagctgctgaagtcgttcggcggcggcgatg cgtatggcagcgcctttgtctatggcctgctcgcaggctggacggtgccgcaggctctgcagcacggcacggcacacgccgct atggtcgtcgcaagccacagctgctcagatgccatgcagacggtcgagcagattgatgctttcatgcaggaacataaagacg agaaagtcatcacggaattggattgggaggcagcattatga

Amino acid sequence (SEQ ID NO:12)

MALISFDENKKRDVVLIGRVTLDFNPNELNRTLDKVKTFSMYLGGSPGNMAVGINKLGKNV

GFIGCVSDDQFGDFVLNYFNERGIDTSQMTRAKNGERMGLTFTEIKSPTESSILMYRDQVA

DLEIAPEDVDEQYIADSKILIVSGTALSKSPSREACLLAVQYAKKHGTRVIFDIDYRPYSWRS

KKDIQIYYSLLASMADVIIGSRDEVNLTEGLDEEATEPADHVIAEKYIEQGAKIVIIKHGKKGSI

AYTADKKAYKVESYHIKLLKSFGGGDAYGSAFVYGLLAGWTVPQALQHGTAHAAMVVAS

HSCSDAMQTVEQIDAFMQEHKDEKVITELDWEAAL

Nucleotide sequence (SEQ ID NO:13) atgccactcgtacatttgacagacctcataagcaagccagacaacacatatgcaattggcgcgttcaatgtctcggatatggag atggccatgggtgccatcaaggcggcagaagagctccatgctccgctgatcctgcagattgcagaaggccgcctgcgctact cgccgctcgacctgcttggccccgtgatgatcgcggccgccaagaagtgctcgatgccgacggccgttcatctcgaccacgg cagcacgatggagacgatcaagcttgcgctcgacctcggcttcacgtccgtcatgttcgacggttcgaaatatccgctcgatga gaacatcgcccgcacgcaggaagtcgtcaagcttgcgaggagctacggcgctgacgtcgaaggtgagatcggccgcgtcg gcggcgcggagggcgactacaagagcgtggatgtcctcgtcacgagcgtcgaggaagccaagcgctttgccgaggaatcc ggcatcgatgcgatggccgtcgcaatcggaacggcacatggcaactacaaggagaagccgcagctccgcatcgaccgcct caaggaaatccatgcggccgtcaagacgccgctcgtcctgcacggcggcacgggcctgacggaagaggatttccggacttg ccttgccaacggcatccagaagatcaacatcgccacggcgtcgtacgacgcttcggcagcgaagataaaggaagtcgctgc agcgaacccgcaggcaaagtacttcgatttcagcgatgccatcgtacagggcacctacgagaatgtaaagaaacacatgca catcttcgggctcgaacagaaggcatga

Amino acid sequence (SEQ ID NO:14)

MPLVHLTDLISKPDNTYAIGAFNVSDMEMAMGAIKAAEELHAPLILQIAEGRLRYSPLDLLG

PVMIAAAKKCSMPTAVHLDHGSTMETIKLALDLGFTSVMFDGSKYPLDENIARTQEVVKLA

RSYGADVEGEIGRVGGAEGDYKSVDVLVTSVEEAKRFAEESGIDAMAVAIGTAHGNYKEK

PQLRIDRLKEIHAAVKTPLVLHGGTGLTEEDFRTCLANGIQKINIATASYDASAAKIKEVAAA

NPQAKYFDFSDAIVQGTYENVKKHMHIFGLEQKA atgaagaagattggttttgtaggactgggcatcatgggcaaaccgatggttcgcaatctcttgaaagcaggctttgctgtgactgt ctacgatatcgtggaggatgcagtcaaggcactggtagaagagggggcaaagggtgcttcttcagcaaaggaagttgcagc ggatcaagacgtcgtcatcacgatggtaccgagtggtccgattgtccgctcgttgctcaagggcgatgacggcatcctggctgg tgtcaaggaaggcacggtcatcgtggatatgagctccgtcacgccggtggaatcgaaggaatttgctgaactggcagcagag aagggatgcgcgttcctcgatgcaccggtcagcggcggtgagccgggtgcagttgcaggttcgctggccattatggtcggcgg tgaagaagctgtcctcaatcaggttcgcgatgtctttgaagcgatgggatcttccatcacactggtcggaccgacgggcagcgg ctcggtgacgaaactggccaatcaggtcatcgtcaacctcaatatcgcagcggtagccgaagcgctcatccittcgaccaagg ccggcgcggatccgaagaaagtctacgaggcaatccgcggcggtctggctggcagcacggtgctggatgctaaggcaccg atgatgttccgccgcaatttcaaaccgggcggaccgatcaagattaacctcaaggacatcacgaatgtcatggatacggcca agaaactcgacctgccactcgtcatgacgggggtgctggagcagatcatgcacagcttgaaggcgacgggccatctgatgg atgatcacagtggcattgtccagttctatgagaatatttccggtgtcgtagtcaagacgcatgaagagtga

Amino acid sequence (SEQ ID NO:186)

MKKIGFVGLGIMGKPMVRNLLKAGFAVTVYDIVEDAVKALVEEGAKGASSAKEVAADQDV

VITMVPSGPIVRSLLKGDDGILAGVKEGTVIVDMSSVTPVESKEFAELAAEKGCAFLDAPVS

GGEPGAVAGSLAIMVGGEEAVLNQVRDVFEAMGSSITLVGPTGSGSVTKLANQVIVNLNIA

AVAEALILSTKAGADPKKVYEAIRGGLAGSTVLDAKAPMMFRRNFKPGGPIKINLKDITNVM

DTAKKLDLPLVMTGVLEQIMHSLKATGHLMDDHSGIVQFYENISGVVVKTHEE

Nucleotide sequence (SEQ ID NO:17) atgggcatcagcatgattgtcttcagcctgatacttttgatgttcttcgcgtatcgtggctattccatcatcttcatcgcaccgattttcgc cgtcgtcgccgccatcggcagcggccacgcctccatgccggtctacagtgagatctatatgacgaaagccgcggagtacatc aagacgtattaccccgtcttcctgcteggcgccgtcttcgccaagatcatggagcagggcgggctcgcggcggccgtggccga caagatcgtctcggcgctgggccgcgacaaggccattctggccgtactgctcggatgcggcgtcctgacgtacggcggtetctc tgtcttcgtcgtcgcctttgtcatgtacccatttgetgccatcctcttcaagcaggctgatatcccgaagcgtctgttgccggggctgct ctggatgggtatcttcacctacagcatggtggccatcccgggcacaccgcagatccagaacatcattccgacgtcgttetttggc acttcgacctggtcggctccggtgcteggcctcatcggtgccgtgctctactteggactggcctggggctggatcagctatcgcca caagaaactcaaggcaaagggtgagggatacggtcaccatgtgctcaatgagccggaggagtcgcgggaggctctgccgg actggcgcctgtcctcactgccgctgcttetegtcatcgtgctgaatctcctgatcagcaatccgttccactgggattgggcgtacc actgggatccggaaagcctcgacagtttcatcccactgcacctctccctgetcgcgggcggcgtcgacaaggtacaggccatc tggtccatcaatgcggctcttatcgtgagctccatcgtcgcggccatcatcggccgcagacggctgagactcaagggcggtctc tcaaagcccatcaacacgggagccatcggctcgacgacggccatcctcaacgtagcttcaggctatgcctacggctgtgtcat cgcagccttgccagccttcacgatcatcaaggaagcattgcteggcctgcacctcggcgacggcccgctgatgtctgccatcgt gacgacgggcatcatgacgggcgtcacgggctettccttgggcggcatgacgattgccctecggcatgctcggacaggagtgg ctggcctgggcgcagcagatcggcatgagtgcagatgtcctgcaccgcatcatctgcatggcctctgagtgcatcgacaccgt gccgcagtcgggcgcactcgtcacactgctegcegtctgcggcctgacgcatcgcgagtcgtattacgacgttgtgatcctgac gctcctgaagacgcttgtcgtettcgcctgcctgggcgtctacctgatgacaggtattgaatga

Amino acid sequence (SEQ ID NO:18)

MGISMIVFSLILLMFFAYRGYSIIFIAPIFAVVAAIGSGHASMPVYSEIYMTKAAEYIKTYYPVF

LLGAVFAKIMEQGGLAAAVADKIVSALGRDKAILAVLLGCGVLTYGGLSVFVVAFVMYPFAA

ILFKQADIPKRLLPGLLWMGIFTYSMVAIPGTPQIQNIIPTSFFGTSTWSAPVLGLIGAVLYFG

LAWGWISYRHKKLKAKGEGYGHHVLNEPEESREALPDWRLSSLPLLLVIVLNLLISNPFHW

DWAYHWDPESLDSFIPLHLSLLAGGVDKVQAIWSINAALIVSSIVAAIIGRRRLRLKGGLSKP

INTGAIGSTTAILNVASGYAYGOCVIAALPAFTIIKEALLGLHLGDGPLMSAIVTTGIMTGVTGS

SSGGMTIALGMLGQEWLAWAQQIGMSADVLHRIICMASECIDTVPQSGALVTLLAVCGLT

HRESYYDVVILTLLKTLVVFACLGVYLMTGIE

Nucleotide sequence (SEQ ID NO: 19) atgaagggagccgaagggctccagggticcaatcagcaagtgatttggggaggaaataatatgticaacaagatgaagaaa cttctttccgtcggtgctgttgtcgcgagtgcggcagtgctgctggcgggctgcggcggtggcagccagcaggcttccagctecttc tggcagcgcagcacaggaaatctccggcaagatctcagcgtcgggctcgacggcactcctgccgctcttgaagccggcaca ggaagccttccaggacaagtacgataaggtgacggtcaacatcgcaggcggcggttcgttcacgggtatgaaccaggtcgc agagggatcggtccagatcggcaactcggatgtcaacctgccggatgagtacaaggacaagggcctcgtcgaccacaagg tcgtcgttgagccgttcgtcttcatcgtcgacaagaacaacaaggtcgacaacatcacgaagcagcaggtcatcgacatcctg acgggcaagatcacgaactggaaggaagtcggcggcgatgaccagccgatcacgctgatccaccgtgcaaagtcctcggg ttcccgtgcgacgatcagcgatgtcgtcctcaagggcgcagccttcacggataacgcagtcatccaggattccaatggtgcagt tcgcgccgctatcgccagcacgccgggctccatcggctatgtcgatgcaccgtatgccgatgattccgtcaagatcctgaagttc gatggcgttgagtattctccggagaacatcatcgccggcaagtatccgatctatggctatggccacatgtacacgaaaggtgag ccgactggcgcggtcaaggcattcatcgactacatcctcagcgatgagttccagaacacgcaggtcgagaagctcggcttcat ccctgtcaacaagatgaagaagtaa

Amino acid sequence (SEQ ID NO:20)

MKGAEGLQGSNQQVIWGGNNMFNKMKKLLSVGAVVASAAVLLAGCGGGSQQASSSSG

SAAQEISGKISASGSTALLPLLKPAQEAFQDKYDKVTVNIAGGGSFTGMNQVAEGSVQIGN

SDVNLPDEYKDKGLVDHKVVVEPFVFIVDKNNKVDNITKQQVIDILTGKITNWKEVGGDDQ

PITLIHRAKSSGSRATISDVVLKGAAFTDNAVIQDSNGAVRAAIASTPGSIGYVDAPYADDS

VKILKFDGVEYSPENIIAGKYPIYGYGHMYTKGEPTGAVKAFIDYILSDEFQNTQVEKLGFIP

VNKMKK

Nucleotide sequence (SEQ ID NO:21) atggaacgggcagcaacaatcggccgccttgacggcaagcagtcaggcggaggtcatgagcgcaggctattctacgacaa gtgcgggcggtatctcttcattgcggctgcctttctcatgaccatcatcatcttttccatcatcttettcgteggtegccagggcctcatg acgttcgcagcggtcagtccgctggagttcttcttcagtgcgagctgggatccgtcgctcggcaagttcggcgcgctctcgttcat cgtgggctcgctggtgacgacactcctttcggttgccatcggcgcgccgcetaggcctgctecggcgccatcttcctcgcgaaggtc gctccggcctggctcaagaacatcatgcgcccggcgacggatctctacgtcgccatcccttcggtcgtctacggctacatcggc ctgatgcetgctcgtgccgtacatgcgcgatgcgttecggcacgacgacgggettcggcgtgetcgcggcgtcgctegtgctegcc atcatgatcatgccgacaatcctctccatcagcacggatgcgctcaatgctgtgccgaagccgctggaggaggcgagcctcg cgctcggcgcgacgtggtggcagacgatggtccacgtcatcgtgcccgctgcagcgcetggcatcctgacggctgtcgtgcte gcgatggcgcgcgccgtcggcgagacgatggccgtgcagatgctcatcggcaacacgccgcagctcatcacctcgctgttct ctccgacggcaacgctgacgagtgacatcgtcgtcgagatgggcaatacgccgtteggctcggtctggggcaatgcgctcttc ctcatggctttcgtgctgctcatcctgtcgctggccatgattcttgtcatccgccgtttcggcacgaggagggtataa

Amino acid sequence (SEQ ID NO:22)

MERAATIGRLDGKQSGGGHERRLFYDKCGRYLFIAAAFLMTIIFSIIFFVGRQGLMTFAAVS

PLEFFFSASWDPSLGKFGALSFIVGSLVTTLLSVAIGAPLGLLGAIFLAKVAPAWLKNIMRPA

TDLYVAIPSVVYGYIGLMLLVPYMRDAFGTTTGFGVLAASLVLAIMIMPTILSISTDALNAVPK

PLEEASLALGATWWQTMVHVIVPAAAPGILTAVVLAMARAVGETMAVQMLIGNTPQLITSL

FSPTATLTSDIVVEMGNTPFGSVWGNALFLMAFVLLILSLAMILVIRRFGTRRV

Nucleotide sequence (SEQ ID NO:23) atgaatgcaaaagtacagaatcaggtggcacgggcgggcctctggtgtacgggattcttcatcctegccctgcttgeggctttcct cggctacatcctctacaagggattgccggtgctctcgccgcacttcattcte:ggcaaatcgagcgacatgatggctggcggcgg cgtcggttcacagcttttcaactcgttctacatgctcttcctctcgatggccatttccattccaatcgcgctcggcgcgggcatctacc tcgcggagtacgcgcgtgagaacaagctgacgaagtgcatccgcctttccgtcgagagcctcgcgacggtgccgtccatcgt actcggcctgtteggcatgatcgtcttcgtcaacatgatgaacatgggcttttccattcteggcggetcgctgacactcgtcctgetg aatctgccgatgctcgtgcgcgtgacggaggaatccatccgcaccgtgccgaggtcgtatgaagaagcgagccttgegctcg gcgcgacgaagctccagacgatcttcaaggtcgtgctgccgagcgcgatgccgggcatcatcacgggcatcacgctgacgg cgggccgtgcactcggcgagacggccatcctgatcttcacggccggcacgacggtatcgcgtcacatgttcgacacggatgtc atggcgggcggcgagacgctggcggttcacctctggtacctcatgagcacgggcctcgtgccggaccgcgaggccatcgcc aacggcatcggcgcactgctgatcctgacgatcctcgtcttcaacttegtcctgctgctgccgatcaagctgctggggcgcaaga caaaagcatga

Amino acid sequence (SEQ ID NO:24)

MNAKVQNQVARAGLWCTGFFILALLAAFLGYILYKGLPVLSPHFILGKSSDMMAGGGVGS

QLFNSFYMLFLSMAISIPIALGAGIYLAEYARENKLTKCIRLSVESLATVPSIVLGLFGMIVFV

NMMNMGFSILGGSLTLVLLNLPMLVRVTEESIRTVPRSYEEASLALGATKLQTIFKVVLPSA

MPGIITGITLTAGRALGETAILIFTAGTTVSRHMFDTDVMAGGETLAVHLWYLMSTGLVPDR

EAIANGIGALLILTILVFNFVLLLPIKLLGRKTKA

Nucleotide sequence (SEQ ID NO:25) atgaaagagacaatcaaatccatgcaggcaatcgcggagccgttettggcattcctgcgctgggaggcgagcagcggtgtca tcctgctcgcctgcgccatcctcgcactcatcgtggcgaattcaccgctggccgaatcgtacgagcatctgctgcattatcccatc gctgtcggagcgggggagtacgtgctggagatgggcctgctgcactggatcaacgacggcctcatggcggtgttcttctttgtca tcggccttgagatcaagcgcgagttcctctacggcgagctgcgcacgtattcggcgatgctgctgcccgtcggcgcggcactcg gcggcatgctcgtgccggccgccatctatgcggcgatcaacttagggctgccgacattcggcggctggggcatcccgatggc gaccgacatcgcctttgegctcggcatcatgaccatcgccgcgcgccaggcaccgctcggcctcgtegtcttcctgacagcact cgccatcgtcgatgacctcggcgccatcgtcgtcatcgcgetgttctacaacacggacctcactgtatcggccttgctgctgggg ctcgtggccgtggctgcegctttcetgetcggccgtttecgcgtgcgcttcctgeccggcctacatggcgctcggcttegtegcctgg ctggccttcctgaaggcgggcatccacccgacgattgegggcgtgctgetcggcctctccatcccggcagcggcggatccgg agaactcgctcctgcacaagctcgagcacgcactcgagccgtggtcggcctatgccatcatgccgatcttcgccttggccaac gctggcgtcgcgatctctctggcgacgtttgacatggcctcgccgatcttcctcggcatcctecgcgggcetctgcctcggcaagcc catcggcatcttcggcgcggtattcgtgctctgcaaggtctttggcctgcagctgccgggcaatgcgacgaagagccagctcgc ggcgacgggcatgctcggcggcatcggattcacgatgtctatcttcatcgcctcgctggccttcacggacagcgcgatgctcga ccttgcgaagatcagcatcctcteggcgtcaatcctctegggcatcctcggtacggctttettcaagctgcagtcgctctteggcgg gggagaaacggcgcaacagtaa

Amino acid sequence (SEQ ID NO:26)

MKETIKSMQAIAEPFLAFLRWEASSGVILLACAILALIVANSPLAESYEHLLHYPIAVGAGEY

VLEMGLLHWINDGLMAVFFFVIGLEIKREFLYGELRTYSAMLLPVGAALGGMLVPAAIYAAI

NLGLPTFGGWGIPMATDIAFALGIMTIAARQAPLGLVVFLTALAIVDDLGAIVVIALFYNTDLT

VSALLLGLVAVAAAFLLGRFRVRFLPAYMALGFVAWLAFLKAGIHPTIAGVLLGLSIPAAADP

ENSLLHKLEHALEPWSAYAIMPIFALANAGVAISLATFDMASPIFLGILAGLCLGKPIGIFGAV

FVLCKVFGLQLPGNATKSQLAATGMLGGIGFTMSIFIASLAFTDSAMLDLAKISILSASILSGI

LGTAFFKLQSLFGGGETAQQ

Nucleotide sequence (SEQ ID NO:27) atgacaaagatcatttttgtgcgccatggccagaccgagtggaatgtgctcggccgctaccagggccagacggacatcgcact ctcgccgctcggcatcgagcaggctgagaagcttgecggcacatttccccgtggacaaggtggaggctgtctactcgagcgac ctcgtgcgcgccatgatgacggcctgctgcgtcgccgaccgcttcggcctgacagtcgaggcgcgccccgagttgcgcgagc tcaacttcggcgactgggagggcctgacgtacgacgaaatcgtcgccaagtggcccgatgccctcaataatttcttccagcatc ccgacgtcctcgagatcccgcacggtgagagcttcccgaagctgcgcgagcgtgcgctcgatgccgtcgagaagatcgtgg cctgccaccctgagcagaccgttgccgtctttgcgcacggcgccattctgcgcaccatcctgacggccgccctgcacatggac ctcaagtacgtctggaccatccgccagttcaacacggccgtcaacatcgtgacgtacaccgagcacggcacgacagtcgaa

Amino acid sequence (SEQ ID NO:28)

MTKIIFVRHGQTEWNVLGRYQGQTDIALSPLGIEQGAEKLAAHFPVDKVEAVYSSDLVRAMM

TACCVADRFGLTVEARPELRELNFGDWEGLTYDEIVAKWPDALNNFFQHPDVLEIPHGES

FPKLRERALDAVEKIVACHPEQTVAVFAHGAILRTILTAALHMDLKYVWTIRQFNTAVNIVTY

TEHGTTVELLNGTGHLKYAQGTVD

Nucleotide sequence (SEQ ID NO:29) atggcaagaactccaatcattgcaggcaactggaagatgaacaacacgatcgtcgagggcaagaacctcgtccgcggcct ggctccgctcgtcaaggatgccaaggtgacggtcgtcgtctgcccgacggctacggctctcgcagctgtcgcagatgcagcac tcggcacgaacatccacgtcggcgcacagaacgttcattgggaagatcacggcgcgttcacgggcgagatctccacgggca tgctcaatgagatcggcgtagattactgcgtcctcggccacagcgagcgccgcggttacttcggcgagacggatgagggcgtc aacaagcgcgctcatgctgctttcgctgcaggcatcacgccgatcatctgctgcggtgagtccctcgagcagcgcgaagctgg tgtatacctcgacttcgtcgctggtcaggtcaaggctgccctcgctggcttccagccggaagaagtagcaaagatcgtcatcgct tacgagccgatctgggctatcggcacgggcaagacggcttccttcgagcaggctgaggaagtctgcgcgcacatccgcaag acggttgccgcagaattcggccaggaagcagctgacggcatccgcatccagtacggcggcagcgtcaagccggctacgat caaagacctcatgaagcagccgaatgtcgatggcgccctcgtcggcggtgcatcgctcaaggctaaggacttcagcgagatc gtaaacttctga

Amino acid sequence (SEQ ID NO:30)

MARTPIIAGNWKMNNTIVEGKNLVRGLAPLVKDAKVTVVVCPTATALAAVADAALGTNIHV

GAQNVHWEDHGAFTGEISTGMLNEIGVDYCVLGHSERRGYFGETDEGVNKRAHAAFAAG

ITPIICCGESLEQREAGVYLDFVAGQVKAALAGFQPEEVAKIVIAYEPIWAIGTGKTASFEQA

EEVCAHIRKTVAAEFGQEAADGIRIQYGGSVKPATIKDLMKQPNVDGALVGGASLKAKDFS

EIVNF

Nucleotide sequence (SEQ ID NO:31) atgaaagcatacttacagatcatgcaggtcatcggccgtgaaatcatcgattcgcgcggcaatccgacggtcgaggcggaag tcacgctcgaggacggctccgtcggccgcgcatctgctcegtegggcgcttcgacgggcgagttcgaggcgctcgagctccg cgacggcgacaaggcgaagtteggcggcaagggcgtctcgaaagctgtcgcgaacatcaatgagaagatcgccccggctc tcatcggtgcggatgcgtcggacatctatgcagtcgatgccatcatgctcaaactcgacggcacggaagacaagtcgaacctc ggcgcgaacgccatcctcgccgtctegctcgcagcggcaaaggccgcggccgtatcgctcgacctcccgctctaccgcttect cggcggcatcagcggcaatcacctgccggtgccgatgatgaacatcttgaacggcggcgcgcatgcgacgaactcggtcga cacgcaggagttcatgatcatgccggccggcgcaccgtccttccgcgagggactgcgctgggcgacggaggtcttccatgcg ctgcaggcgctgctcaagaaggaagggcagacgacggctgtcggcgatgagggcggctttgctccgaacctcaagagcga cgaggacacgatcgagcacatcctgacggccatccgcaatgcgggttacgagccgggccgcgacttcgtgctggcgatgga tgcggcttcgtcggagtggaagagcgagaagggcaagggcttctacaagcagccgaagtcgggcaaggagttcacgtcgg atgagctcatcgcgcactggaagagcctcatcgagaagtacccgatctactccattgaggacggcctcgatgaggaggactg ggaaggctggcagaagatgacgaaggagctcggcgacaaggtacagctcgtcggcgatgacctctttgtcacgaacacga agcgcctgaagaagggcatcgagctcggctgcggcaacagcatcctcatcaagctcaaccagatcggcacgctgtcggag acgctggaggccatcaagatggcacatgaggcgggctacacggccatcgtctegcaccgttcgggcgagacggaggacac gacgatcgcggacctcgctgtcgcgctcaacacgaaccagatcaagacgggcgccccgtcccgctcggagcgcegtcgcca agtacaaccagctgctgcgcatcgaggaagagctcggcgcaagcgcggtctatccgggcaaagcagcttttagattccaga agtaa

MKAYLQIMQVIGREIIDSRGNPTVEAEVTLEDGSVGRASAPSGASTGEFEALELRDGDKAK

FGGKGVSKAVANINEKIAPALIGADASDIYAVDAIMLKLDGTEDKSNLGANAILAVSLAAAKA

AAVSLDLPLYRFLGGISGNHLPVPMMNILNGGAHATNSVYDTQEFMIMPAGAPSFREGLRW

ATEVFHALQALLKKEGQTTAVGDEGGFAPNLKSDEDTIEHILTAIRNAGYEPGRDFVLAMD

AASSEWKSEKGKGFYKQPKSGKEFTSDELIAHWKSLIEKYPIYSIEDGLDEEDWEGWQKM

TKELGDKVQLVGDDLFVTNTKRLKKGIELGCGNSILIKLNQIGTLSETLEAIKMAHEAGYTAI

VSHRSGETEDTTIADLAVALNTNQIKTGAPSRSERVAKYNQLLRIEEELGASAVYPGKAAF

RFQK

Nucleotide sequence (SEQ ID NO:33) atgaacaagaaaaccatcaaagacgttgacgtaaacggcaagaaagtattcgtccgcgtcgactacaatgtcccgttcgacg acaagatgaacatcacgaacgacacgcgcatggtccgcacgctgccgaccctgaactacctgctcgaccacggtgcagctc tcgtcatcgcctgccacatcggccgtccgaccgaggcgcgcgaggacaagttctccacaaagtacctcgtcaagcacctctcc gagctgctcggccgcgatgtcaagtgggcctccgactgcgtcggcgctgaggcagatgccgcaaaggctgcgctgaagccg ggcgaagtcctgctgcttgagaacctccgttaccacaaggaagagaagaagaacgatcccgagttcgcgaagcagctcgct tccggttgcgatctcgcagtcgacgatgctitcggtgtttcccaccgcgctcatgcttcgaacgcaggcgttccgaagtacatcga gacggttgctggcttcctgatggaaaaggaaatcaactacatcggcaagacgctcgagaacccgcagcatccgttcgtegcc attatcggcggtgcaaaggtctccgataagatcggcgtcatcagcaacatgatcgacaaggttgacacgatcatcatcggcgg cggcatggctcatacgtttgatgcagccaagggcctgccgattggcgattccctctgcgagccggacaagtacgatctcgctcg tgagctgctcaagaaagcagaagacaagggcgtcaaggtcgtcctgccggtcgacctcgtcattgccgacaagttcgctgcc gatgccaacacgaagacggttgacgtcgacaaagtaccggatggctggcaggcactcgattccggcgagaagacgtcgga agagtacacgaaggctcttgaaggcgctaagacggtcatctggaacggaccgatgggcgtattcgagtttgatgcttttgcaaa aggcacgctcgctgttgctaaggctgtcgccaaggctacggaaaatggcgctatctccatcgtcggcggcggcgactccgttg cagccctcaagaagacgggcctgacggacaagatctcgcacgtctccacgggcggcggcgctacgctcgagttcctcgaag gcaaagagatgccgggcatcgcagcactggctgacaaataa

Amino acid sequence (SEQ ID NO:34)

MNKKTIKDVDVNGKKVFVRVDYNVPFDDKMNITNDTRMVRTLPTLNYLLDHGAALVIACHI

GRPTEAREDKFSTKYLVKHLSELLGRDVKWASDCVGAEADAAKAALKPGEVLLLENLRYH

KEEKKNDPEFAKQLASGCDLAVDDAFGVSHRAHASNAGVPKYIETVAGFLMEKEINYIGKT

LENPQGHPFVAIIGGAKVSDKIGVISNMIDKVDTIIIGGGMAHTFDAAKGLPIGDSLCEPDKYD

LARELLKKAEDKGVKVVLPVDLVIADKFAADANTKTVDVDKVPDGWQALDSGEKTSEEYT

KALEGAKTVIWNGPMGVFEFDAFAKGTLAVAKAVAKATENGAISIVGGGDSVAALKKTGLT

DKISHVSTGGGATLEFLEGKEMPGIAALADK

Nucleotide sequence (SEQ ID NO:35) atgttaaagaagacgaaaattatctgcacgcagggtcctgctacggagagaccgggcgtagtcgatgcactgattgcaaacg gcatgaactgtgcacgctttaacttctcccatggtgaccacgcagagcacctcaaccgcatcaacatggtgcgcgaggctgcc aagaaggccggcaaggtcatttccctgattctcgatacgaagggaccggagatgcgcctcggcgagttcaaggacggcaag gtcatgctcgagaagggcaatcagttcacgctgacgtatgaggacatcccgggcgatgagacgcatgtctccgtcaaccaca agggcctctacacggaagtcaagccgggtgacacgctgctcctctctgatggcctcgtagcactcaaggtcgatgagatccgc ggcaaggacatcatcacgacgatccagaacagcggcaagatgagcacgaagaagcgcgtcgctgctccgggcgtatccet cggcctgccgccgatctcggagcaggatgcgaaggacatcatctteggctgcgagcaggacctcgatttegtegctgcttccttt atccagcgtccggaggacgtcctggccatccgcaagctcatcgaggagcacaatggccacatggagatcatgccgaagatc gagaacctcgaaggcgtcaagaacttcgatgcgattctcgaagtctccgacggcatcatggtcgctcgcggtgacctcggcgtt gaggttccggccgaggacgttccgctgatccagaaagagatcatccgcaagtgcaacaaggctggcaagccggtcatcgtc gctacgcagatgctcgactccatggagcgcaacccgcgcccgacgcgcgctgaggtctccgatgtcggcaacgccatcctc gatggtacggatgccatcatgctctccggcgagacggcttccggcgattacccggtcgaggctgtttccacgatgaaccgcatc gcttgccgcatcgaggagtccctcgagtacaagaatctcttcgttgagcgcggcttcgagcacagccagagccgcacgcgcg ccgtcgcacatgctacggtacagatggcttacgagctcgatgtcccggctatcatcacgccgaccgacagcggctacacgac gaagatcgtatcccgttaccgtccgaaagcagctatcgttgcctacacgccgcatgagaaggtcgtccgccagctcaacctcc gttggggcgtatacccgatcctcggcacgcagtggaaggacgtcgacgagatgattgcgaacgctgtttccgcagctgtcaag gacggcttcgtgaagcgcggcgacacgacgatcatcacgtccggcatcaagctccagagcaagacgagcgtcggcaaca acacgaacatgatccgcgtctacaagatctga

Amino acid sequence (SEQ ID NO:36)

MLKKTKIICTQGPATERPGVVDALIANGMNCARFNFSHGDHAEHLNRINMVREAAKKAGK

VISLILDTKGPEMRLGEFKDGKVMLEKGNQFTLTYEDIPGDETHVSVNHKGLYTEVKPGDT

LLLSDGLVALKVDEIRGKDIITTIQNSGKMSTKKRVAAPGVSLGLPPISEQDAKDIIFGCEQD

LDFVAASFIQRPEDVLAIRKLIEEHNGHMEIMPKIENLEGVKNFDAILEVSDGIMVARGDLGV

EVPAEDVPLIQKEIIRKCNKAGKPVIVATQMLDSMERNPRPTRAEVSDVGNAILDGTDAIML

SGETASGDYPVEAVSTMNRIACRIEESLEYKNLFVERGFEHSQSRTRAVAHATVQMAYEL

DVPAIITPTDSGYTTKIVSRYRPKAAIVAYTPHEKVVRQLNLRWGVYPILGTQWKDVDEMIA

NAVSAAVKDGFVKRGDTTIITSGIKLQSKTSVGNNTNMIRVYKI

Nucleotide sequence (SEQ ID NO:37) atggcagtaaaagttgctatcaatggttttggccgtatcggtegtctcgcattccgtcagatgttcgatgctgagggttatgaagtcg ttgcaatcaacgatctcacgagcccgaaaatgctcgcttacctgctgaagtacgattcttcccagggcaagtacgagtatgctga cacggttgaggctggcgaagacagcatcacggtcaagggcaagacgattaaaatctatgccgagaaagatgcaaagaac atcccctgggcgaagcatgatgtagatgtcgttctcgagtgcacgggcttctacacgtccaaggaaaaggcttccgcacatctc gaagctggcgctaagaaagtcgtcatctccgctccggcaggcaaggacctcccgacgatcgtgttcaacacgaaccacaag tccatcccggcaggcacgaaaatcatctccgctgcatcctgcacgacgaactgcctcgcaccgatggcaaaggccctcaatg accttgctccgattcagagcggcatcatgcagacgatccacgctttcacgggcgaccagatgacgctcgatggcccgcagcg caagggtaacctccgccgcagccgtgetgettccgagaacatcgttccgacgtcctccggcgcagctaaagctatcggcctcg ttcttccggaactcgatggcaagctcatcggtgctgcacagcgcgttccgaccccgacgggttccacgacgctcctctacgctgt tgtcaagggcaacgttacggttgacgaagtcaatgcacagatgaagaaggagtccacggagtccttcggctacaacacggat gacattgtatccaaggatgttgtcggtatgcgttatggctccctgttcgatgctacgcagacgatggtcagcccgatggctgatgg caacacgctcgttcaggttgtatcctggtacgacaacgagaactcctacacgagccagatggttcgcacgatcaagtacttcgc tgaggaagtcaagtaa

Amino acid sequence (SEQ ID NO:38)

MAVKVAINGFGRIGRLAFRQMFDAEGYEVVAINDLTSPKMLAYLLKYDSSQGKYEYADTVE

AGEDSITVKGKTIKIYAEKDAKNIPWAKHDVDVVLECTGFYTSKEKASAHLEAGAKKVVISA

PAGKDLPTIVFNTNHKSIPAGTKIISAASCTTNCLAPMAKALNDLAPIQSGIMQTIHAFTGDQ

MTLDGPQRKGNLRRSRAASENIVPTSSGAAKAIGLVLPELDGKLIGAAQRVPTPTGSTTLL

YAVVKGNVTVDEVNAQMKKESTESFGYNTDDIVSKDVVGMRYGSLFDATQTMVSPMADG

NTLVQVVSWYDNENSYTSQMVRTIKYFAEEVK

Nucleotide sequence (SEQ ID NO:39) atgaaaaaattccaagtcgtcgtgaagtgctcactcggtatccatgcgcgtcccgcagctcagatcgcgcaggcatgcagcaa cctgcgggcggcggtgacgctcgaggtcgataatgagactgcccagggcaacaacgtgctggagatcttgaacctccacgct ccgaaaggcgcaacggtcaatgtcaccgtggacggccctgatgaggaagaggctgcacagcagatccaggctgttttcgat gccatgggcccgaaggagaagaagggctctgtcctcaaggtcgcctttttcggcacgaaagactatgaccgcctctatttcagc gagctcgcaaaggacaagggcgagggcacgtacaacgtcgaactcaagtatttctcgagccgcctgacggatgagacggc acatctcgccaacggctatgacgctgtctgcatcttcgtcaacgacgaggcaccgcgttctgtcatcgagcagctgcatgacgg cggcgtccgcctgatcctcctgcgctgcgccggcttcaacaatgtcgacaagaaggccgctgccgagtacggcatcacggtc ctgcgcgtaccggcttactccccgtacgcagtggcagagcatgccatggcgacgctgcaggctgcaaaccgccgcctgcac aaggcatacaacaaggtgcgcgacaacaacttcgacctcacgggcctgctcggcgtcgatctccacaacaaggtcgccggc atcctcggcacgggccgcatcggccagtgcatggcgcgcatctgcaagggctacggcatgacggtcatcggctgggatgcgt tcccgaacaagaagctcgaggaagaggggctgctcacctatgcttcgaaggaagaggtcctgaagcgctetgacctcatctc cattcacgcaccgctcatcatgggcgaaggcggcacgtatcatctcattgatgagaaggccatctccctcatgaaggacgatgt catgctcacgaatgctgcacgcggcggcctcatcgatacggaagcgctcattgccgcgctcaagaagggcaagttccatgcg gttgegctcgacgtctacgagggcgaggatgccaatgtctacacggaccacagcttcgacgtcccgacggaggatgtcacgg gccgtctgctcatgttcccgcaggtcatcctcacgagccatcaggcattctttacgcgcgaggcactgcaggccatcgcgacgg tgacgatggagaacgcccgcaatttcaacgagggccgtccgttcggtgctgctgaggtgaaataa

Amino acid sequence (SEQ ID NO:40)

MKKFQVVVKCSLGIHARPAAQIAQACSNLRAAVTLEVDNETAQGNNVLEILNLHAPKGATV

NVTVDGPDEEEAAQQIQAVFDAMGPKEKKGSVLKVAFFGTKDYDRLYFSELAKDKGEGT

YNVELKYFSSRLTDETAHLANGYDAVCIFVNDEAPRSVIEQGLHDGGVRLILLRCAGFNNVD

KKAAAEYGITVLRVPAYSPYAVAEHAMATLQAANRRLHKAYNKVRDNNFDLTGLLGVDLH

NKVAGILGTGRIGQCMARICKGYGMTVIGWDAFPNKKLEEEGLLTYASKEEVLKRSDLISIH

APLIMGEGGTYHLIDEKAISLMKDDVMLTNAARGGLIDTEALIAALKKGKFHAVALDVYEGE

DANVYTDHSFDVPTEDVTGRLLMFPQVILTSHQAFFTREALQAIATVTMENARNFNEGRPF

GAAEVK

Nucleotide sequence (SEQ ID NO:41) atgagcaaaaagatgaaaaccatggacggcaacacagctgccgcctacatctcctatgctttcaccgacgtcgcggcgatct acccgattacgccgtcctcgccgatggctgagcatgtagatgaaatggctgccaagggagcgaagaatctcttcggccagaa ggtcaaggtcatcgagctgcagtctgaggccggcgctgccggcgctgtgcacggctcgctgcaggccggtgcactgacgac gacgtacacggcttcccagggcttcttgctgatgatcccgaatctctacaaggtagccggcgagctgttgccgggcgtcttccac gtctccgcgcgcgcactcgctgccaactccctgaacatcttcggcgaccaccaggatgtcatggccgcacgccagacgggtt gcgccatgctcgccgaggcgagcgtccaggaggtcatggacctetcggccgtcgcacacctcgtcgccatcaagggccgcg tgccgttcatcaacttcttcgacggcttccgcacgtcgcacgagatccagaagatcgagacgattgactacgaagacctcgca aagctgctcgactgggatgccgtcaaggccttccgccgccgcgctctgaacccggaccacccggtcctgcgcggctccgcga cgaacccggacatctacttccagtcgcgtgaagcagccaacagcttctacgatgcgctgccagagctcgtcgaggaggccat ggctgacctcgcgaaggtcacgggccgcgagcaccatctctttgactactatggcgccaaggatgccgaccgcatcatcatcg cgatgggctccgtctgccagacggtccaggagacggtcgactacctcaacgcgaagggggagaaggtcggcctgctgaac gtacacctctaccgtccgttctccatcgagcacttcttcaagttcctgccgaagaccatcgagaaagtcgccgtcctcgaccaca cgaaggagccgggttegcteggcgagccgetctacctcgatgtcaaggcagccttctatcattccgacatgcacccgacgatc atcggcggccgcttcggcctcggcggcaaggacacgacgccggaccagatcttegccgtctttgaagagctcaagaaagac gcgccgaaggacggtttcacgatcggcatcgacgacgatgtcacgcacacgagcctgacgccggcgctgacggatgtcga cctcacgccggaaggcacgacggcctgcaagttctggggcctcggctcggatggcacggtcggcgccaacaagagcgcca tcaagatcatcggcgacaagacggacatgtacgcccaggcgtacttcgcctatgactccaagaagtcgggcggcatcacgat gtcgcacctgcgcttcggcaagtccccgatcacgagcccgtacctcatcaacaaggccgacttcatctcctgetcgcagcagtc gtacgtctacaagtacgacctgctcgccggcctcaagaagggcggcacgttcctcctcaacacggtctggagcgacgagaa gctcacgaagcacctgccggcagccatgaagcgctacatcgccaagaacgagatccagttctacacggtcaacgetgtctcc atcgccaagggcctcggcctcggcggccgcttcaacatggtcatgcagtccgcgttcttcaagctcgcgaacatcatcccgatc gagacggccgtgacctacctcaaggaagccgtcgtcacctcgtacggccgcaaaggccagaacatcgtcgacatgaacaa cggcgccatcgaccagggcatcgaggccctgcacaaggtcgaggtgccggcatcgtgggctgatgctgaagacgagccgc aggagaagcgcgacctgccggagttcatcaccgaggtccaggaagtcatgaaccgccaggaaggcgacaagctgccggt ctcgaagttcgccggcgaccgcgccgacggcacgtacccgctcggcggcgccgcctacgagaagcgcggcacggccatc aacgtgccggtctggaacgcccagaagtgcatcggctgcaacaagtgctcctatgtctgcccgcacgcttcgatccgtccggtc ctcacgaccgacgaagagctcgctgcagcaccggagggcttcccgtccaaggaagtccgcgccgtcaaggactaccacttc acggtggctgtctccacgatggactgcctcggctgcggcaactgcgcgcaggtctgcccggtcaaggcgctcgacatgacgc cgcttgacgacgacctcaaggcaaagcaggcttacttcgactacggcgtcgacacggagaaagtcgcgccgaagaagaac ccgatgaagaaagagaccgtcatcggcagccagttcgagcagccgctcatcgagttctccggcgcctgcgccggctgceggc gagacgccgtacgccaagctcatcacgcagctcttcggcgaccgcatgatgattgccaacgccacgggctgcacctccatct ggggcggcagcgcaccggccatgccgtacacgacgaacgccaagggccacggcccggcttgggacaactccctgttcga ggacaacgcagagttcggcctcggcatgttccteggcacgcagtccgtccgcaatggcctcgccgatgacgccaagaaggc catcgaagaaggtcttggcagcgaagacctccaggcagccctcaaggactgggtagagaacctcgacaacggcaacggc acgcgcgaccgcgccgaccgcctcgaagccctgctcgcagccgagaagggtgacaatgcgctgctcaacaagctctacga gaaccgcgactacttegtcaagcgctcccagtggatcttcggcggcgacggctgggcctacgacatcggctacggcggcgtc gaccacgtcctcgcctccggcgcagacgtcaacgtcttcgtcttcgacaccgaagtctactccaacaccggcggccaggcctc caaggccacgccggcagcagcaatcgcacagttcgccgcaaccggtaagaagacccgcaagaaggatctcggcctcatg gccaagacctacggctacgtctacgtcgcccaggtcgccatgggcgcagaccagaaccagctgctcaaggccatcaccga ggccgaggcttatccgggcccgtccctcatcatcgcctacgcaccgtgcatcaaccacggcatccgcaagggcatgggctgc agccagctcgaggagaaactcgccgtagagtgcggctactgggcaaactaccgctacaacccgcagctcgtcggcaccga caagaacccgttcagcctcgactccaaagagccggacttctccaagttccaggacttcctcatgggcgagaaccgctacatca acctcaagcgcaccttcccagaagcagccgaagccctctttgagaagacccagcgcgacgccgagatccgctacaacaac tacaagaccctcgccggcaaataa

Amino acid sequence (SEQ ID NO:42)

MSKKMKTMDGNTAAAYISYAFTDVAAIYPITPSSPMAEHVDEMAAKGAKNLFGQKVKVIEL

QSEAGAAGAVHGSLQAGALTTTYTASQGFLLMIPNLYKVAGELLPGVFHVSARALAANSL

NIFGDHQDVMAARQTGCAMLAEASVQEVMDLSAVAHLVAIKGRVPFINFFDGFRTSHEIQ

KIETIDYEDLAKLLDWDAVKAFRRRALNPDHPVLRGSATNPDIYFQSREAANSFYDALPEL

VEEAMADLAKVTGREHHLFDYYGAKDADRIIAMGSVCQTVQETVDYLNAKGEKVGLLNV

HLYRPFSIEHFFKFLPKTIEKVAVLDHTKEPGSLGEPLYLDVKAAFYHSDMHPTIIGGRFGL

GGKDTTPDQIFAVFEELKKDAPKDGFTIGIDDDVTHTSLTPALTDVDLTPEGTTACKFWGL

GSDGTVGANKSAIKIIGDKTDMYAQAYFAYDSKKSGGITMSHLRFGKSPITSPYLINKADFIS

CSQQSYVYKYDLLAGLKKGGTFLLNTVWSDEKLTKHLPAAMKRYIAKNEIQFYTVNAVSIA

KGLGLGGRFNMVMQSAFFKLANIIPIETAVTYLKEAVVTSYGRKGONIVDMNNGAIDQGIEA

LHKVEVPASWADAEDEPQEKRDLPEFITEVQEVMNRQEGDKLPVSKFAGDRADGTYPLG

GAAYEKRGTAINVPVWNAQKCIGCNKCSYVCPHASIRPVLTTDEELAAAPEGFPSKEVRA

VKDYHFTVAVSTMDCLGCGNCAQVCPVKALDMTPLDDDLKAKQAYFDYGVDTEKVAPKK

NPMKKETVIGSQFEQPLIEFSGACAGCGETPYAKLITQLFGDRMMIANATGCTSIWGGSAP

AMPYTTNAKGHGPAWDNSLFEDNAEFGLGMFLGTQSVRNGLADDAKKAIEEGLGSEDLQ

AALKDWVENLDNGNGTRDRADRLEALLAAEKGDNALLNKLYENRDYFVKRSQWIFGGDG

WAYDIGYGGVDHVLASGADVNVFVFDTEVYSNTGGQASKATPAAAIAQFAATGKKTRKKD

LGLMAKTYGYVYVAQVAMGADQNQLLKAITEAEAYPGPSLIIAYAPCINHGIRKGMGCSQL

EEKLAVECGYWANYRYNPQLVGTDKNPFSLDSKEPDFSKFQDFLMGENRYINLKRTFPEA

AEALFEKTQRDAEIRYNNYKTLAGK

Nucleotide sequence (SEQ ID NO:43) atggtagatatcctcgatcgtgtgcgcaacaaggcgctgcagtccaagatcgtgacaccggaggaagcggcagacttcatca agccgggcatgacccttgcgacgagcggcttcacatccteggcctacccgaaggcggtgccgctcgctctcgcggaccgcat gaagaaggacccgttcacggtcaacatcatgacgggcgcttcgacgggcccggagttcgatgaagcgctcgccteggtcca cggcatcaagaaacgcctgccgttccagacggacaaggtgctgcgcagccagatcaacgacggcacggtcgattacatcg acatacatctgtcggaggtcgcgcagctctcgegctgcggctaccteggccatctcgacgtcgccgtcatcgaggcctgcgcc atcacggaggagggcaacatcatcccgacgacggccgtcggcaactcggcctcgttegtgcagacggccgacaccgtcatc atcgaggtcaacaacgcgcagccgctggagttcgagggcatgcacgatgtctacctgccgctcgacccgccgaaccgtctgc ccatcccgatcgtgcgcgtcgacgaccgcatcggcacgccgtacatcccgtgcccgcaggacaagatccgctacatcgtgcc gtgcgacatcgcggaccacacgcgctcgctcgcgccgctcgacgcgacggcgcagcagatggctgacctgacgattgactt cctcaagcgcgagataaaggctggccgcatgccgaagaacctgctgccgatacagtcgggcgtcggcaatgtcgccaatgc cgtcacggcgggctttgtccgcteggacttccgcgacctcacggtctacacggaggtcatccaggacggcatgctcgacctcat cgatgcgggcaagctcaacttcgcctcgggcacggccttctegccgtctcctgagggcatggcgcgcttcttcaaggacattga gaagtacaagaagtacatgatcctgcgcccgcaggagatctcgaacagcgcggaggtcatccgccgcctcggcgtcattgc gatgaacacggccgtcgaagtcgacatctacggcaacgtcaactcgacgcacatcgcgggcacgcacatgatcaacggca tcggcggcagcggcgacttcgcgcgcaacgcctacctgaccatcttctacacgccgtcggtggccaagggcggcaagatctc ggccgtcgtgccattctgetcgcatgttgaccagccggagcacgacgtcgacgtcatcatcacggagcagggcgtggccgac ctgcgcggcaagtcgccgcgccagcgcgccaaggagatcatcgagaactgcgcgcaccccgacttccgcccaatgctgcg cgactatttccagcgcgccgacgcgaagacgaaccacgcgcacacgccgcacctcctcgatgaggccttetcgttccaccag cgctatctggagacaggcagcatgaagcgcgagagtcaggaagatacaggaaaggtgtga

Amino acid sequence (SEQ ID NO:44)

MVDILDRVRNKALQSKIVTPEEAADFIKPGMTLATSGFTSSAYPKAVPLALADRMKKDPFT

VNIMTGASTGPEFDEALASVHGIKKRLPFQTDKVLRSQINDGTVDYIDIHLSEVAQLSRCGY

LGHLDVAVIEACAITEEGNIIPTTAVGNSASFVQTADTVIIEVNNAQPLEFEGMHDVYLPLDP

PNRLPIPIVRVDDRIGTPYIPCPQDKIRYIVPCDIADHTRSLAPLDATAQQMADLTIDFLKREI

KAGRMPKNLLPIQSGVGNVANAVTAGFVRSDFRDLTVYTEVIQDGMLDLIDAGKLNFASGT

AFSPSPEGMARFFKDIEKYKKYMILRPQEISNSAEVIRRLGVIAMNTAVEVDIYGNVNSTHIA

GTHMINGIGGSGDFARNAYLTIFYTPSVAKGGKISAVVPFCSHVDQPEHDVDVIITEQGVAD

LRGKSPRQRAKEIENCAHPDFRPMLRDYFQRADAKTNHAHTPHLLDEAFSFHQRYLETG

SMKRESQEDTGKV

Nucleotide sequence (SEQ ID NO:47) atgaagaacattcgcaagatcttggtgccgaaccgcggcgagattgccatccgcattttccgcgcctgccacgagatgggcat ccgcacggtcgcggtctactcgaaagaagatgtcctgtcgctgcatcgcagccgcgccgatgaagcgtatctcgtcggcaag ggcaagaagccagtcgatgcctacctcgacatcgaggacatcatccgtatctgcaaagagcacgatgtcgatgccatccatc cgggctacggcttcctctccgagaacgcacagctggccaagcgctgcgaggatgagggcatcatcttcatcggcccgaaagt tgagcacctgcagatgttcggcgacaaggtcaacgcgcgcatccaggcagagcgcgccgacatcccgatgatcccgggca cgaacggtgccgtcaaggatttcgctgaggtcaaggccttcgctgagcgcgtcggcctgccgatcatgatcaaggccatcaac ggcggcggcgggcgcggcatgcgccgcgtcgaccgcatggaagacctcaaagaggcgtacgatgaggcgcgctcggag gccaagcgtgccttcggcgatgaggatgtctacgtcgagaagtgcatcctaaacccgaagcacatcgaagtgcagatcatgg gcgatgaacacggcaatgtcatccacctcaatgagcgcgactgctccatccagcgccgccaccagaaagtcatcgagatgg caccggcatggtcgctgccgaagaagctgcgccagaatatctgcgctgctgcgctgaagatcatgaagaatgtccactacgtc aacgccggcacagtcgaattcctcgccgaccaggatgaggagcacttctacttcatcgaagtcaacccgcgcgtccaggtcg agcacacggtcaccgaggccatcacggacatcgacatcgtcaagacgcagatcctcgtcgccgagggccatgcgctctccg acccagagatcggcatcaagagccaagaagacatcccctgcaacggcgtggccatccagtgccgcatcacgacggagga cccgcagaacaacttcatgccggacaccggcaagatcaacgactaccgcagcggcggcggccctggcatccgcctcgatg ccggcacggcctacacgggcgccgtcatcacgccgtactacgactccctgctcgtcaaggtcacggcgcatgccaacaacg ccccggagacaatctaccgcatgctgcgctgcctcgatgaattccgcatcggcggcgtcaagacgaacatctacttcctcaag aacatgctgctcgacaagaacttccaggctggcagctgcaacgtcaactacatcgaccaccatccggacctgctcaacgccc cgcaggtcatcgatgagccggcagccggcctgctcgcctacatcggtgaggtcacggtcaacggcttccacggcaacggctc aaacccgaagccgcgcttcgagacgccggtgaagctcaatgccgccgacgaagcctgcccgtccggcacgcgccagctcc tagaggagctcggccccgagaagttctccaagtggatccaggaccagaagcaggtcctgctgatggacacgacgtaccgcg atgcccatcagtccctgctcgccacgcgcatccgcacgcgcgacatcatgcaggccatccactacacggcctgcaaggtccc gcagatctacgcctttgaggactggggcggcgcgacgttcgatgtegcctaccgtttcctc:gacgaggacccgtgggagcgcc tgcgcaagatgcgcgaggctgcgccgaacatcctgttccagatgttgacgcgcggcgccaacaccgtcggctacacgaact atccgcctgaagtcgtgcgccagttcctegccctcgcggccaagaacggcgtcgatgtcttccgcatcttcgactgcctgaacc agctcgaccacatgacgctgtcgattgacgaagtccgcaagcagggcaagctcgcggagacggccttctgctacacgggcg atatccttgacgacggccgccagaagtacacgctgaagtactacacgaatctcgccaaggagatggaaaaggccggtgcc aacatcatcgccatcaaggatatggccggcctcctgaagccagaagcggcctacaccctgatctcggccctcaaggatgctgt cgacctgccgattcacctgcacagccacgagggtggcggctgcacgctctacacctacgccaaggcggcagaggccggcg tcgacatcgtcgatgtcgccacgagcgccctctccaacggcacgagccagccgtccatgacggccttcatccaggcgctctcc aacaacccgcgccagccgcagatggacatcgaggaactcgagacgattgaccgctactggcaggtcgtccgcgcctactac gcgggtgtcgacggcaagatgacgagcccgaacacgacggtcttccagcacgagatgcctggcggccagtacacgaacct gcgccagcaggcgaagggcgtcggcctcggcgacagatggccggaagtctgccgcatgtacgccaaggtcaacgagatgt tcggcgatgtcatcaaggtcacgccgtcctcgaaagtcgtcggcgacatgacgctcttcatggtccagaacaacctgaccgag aaagatatctacgagcgcggcgagacgatggacttcccgaaatccgtcgtcgacttettcgacggcaagctcggcgtccccta cggcggcttccccgagaagctccagaagatcatcctcaggggcgagcagccgcacctcgagacgccgcccgccccgatcg accaggagaaggtcacgcaggacatgaaggccctgcgcatgccggagacggaagaggcgcgctcgagctactgcatcta cccgaaggtctacaaggactacatccagcgctaccatcagtacggcgacctttccatcctcgacacgccgacgtacttcttcgg catgaagccgggcgaggagagctggctgcgcatcggcggcaagatggtcctcatccgcatgaactacatcacgccgccgtc ggatgatggcttccgcgagatccagttcgaggtcaacggcatgccgcgcgagatccgcgtgcgcgataaggcggcttcgga aggcgcggcgatcatccgccaggccgacccgactgtcccgggcgaagtagccgctacgctctctggetctgtcctgcgcctca tcgcagccaagggcgatgtcgtcaagaaaggcgacccgctgatggtcacggaggccatgaagatggagacgacgatcac cgcgccgattgccggcatcgtcaaggaggtctgtgtcgcagcaggcagccgcatcacttccggcgacctcctcgctgtcatcg aataa

Amino acid sequence (SEQ ID NO:48)

MKNIRKILVPNRGEIAIRIFRACHEMGIRTVAVYSKEDVLSLHRSRADEAYLVGKGKKPVDA

YLDIEDIRICKEHDVDAIHPGYGFLSENAQLAKRCEDEGIIFIGPKVEHLQMFGDKVNARIQ

AERADIPMIPGTNGAVKDFAEVKAFAERVGLPIMIKAINGGGGRGMRRYDRMEDLKEAYD

EARSEAKRAFGDEDVYVEKCILNPKHIEVQIMGDEHGNVIHLNERDCSIQRRHQKVIEMAP

AWSLPKKLRQNICAAALKIMKNVHYVNAGTVEFLADQDEEHFYFIEVNPRVQVEHTVTEAI

TDIDIVKTQILVAEGHALSDPEIGIKSQEDIPCNGVAIQCRITTEDPQNNFMPDTGKINDYRS

GGGPGIRLDAGTAYTGAVITPYYDSLLVKVTAHANNAPETIYRMLRCLDEFRIGGVKTNIYF

LKNMLLDKNFQAGSCNVNYIDHHPDLLNAPQVIDEPAAGLLAYIGEVTVNGFHGNGSNPK

PRFETPVKLNAADEACPSGTRQLLEELGPEKFSKWIQDQKQVLLMDTTYRDAHQSLLATRI

RTRDIMQAIHYTACKVPQIYAFEDWGGATFDVAYRFLDEDPWERLRKMREAAPNILFQML

TRGANTVGYTNYPPEVVRQFLALAAKNGVDVFRIFDCLNQLDHMTLSIDEVRKQGKLAET

AFCYTGDILDDGRQKYTLKYYTNLAKEMEKAGANIIAIKDMAGLLKPEAAYTLISALKDAVDL

PIHLHSHEGGGCTLYTYAKAAEAGVDIVDVATSALSNGTSQPSMTAFIQALSNNPRQPQM

DIEELETIDRYWQVVRAYYAGVDGKMTSPNTTVFQHEMPGGQYTNLRQQAKGVGLGDR

WPEVCRMYAKVNEMFGDVIKVTPSSKVVGDMTLFMVQNNLTEKDIYERGETMDFPKSVV

DFFDGKLGVPYGGFPEKLQKIILRGEQPHLETPPAPIDQEKVTQDMKALRMPETEEARSSY

CIYPKVYKDYIQRYHQYGDLSILDTPTYFFGMKPGEESWLRIGGKMVLIRMNYITPPSDDG

FREIQFEVNGMPREIRVRDKAASEGAAIIRQADPTVPGEVAATLSGSVLRLIAAKGDVVKKG

DPLMVTEAMKMETTITAPIAGIVKEVCVAAGSRITSGDLLAVIE

Nucleotide sequence (SEQ ID NO:49) atgaaggtaacagttgttggtgcaggtaatgttggtgcaacggtcgcaaacgttcttgctacgaagaagttctgcagcgaggttgt tcttgttgatatcaaggaaggcgttccgcagggcaaggccatggatatcatgcagacggctcacatgctgaactttgacacgac ggtaacgggcgttacggctctgccgaacgatccggaaggctatgctccgacggctggttctgatgttgtcgttgtcacgtetggc atgccgcgcaaaccgggcatgagccgtgaggacctcatcggcgtcaacgctaagatcgtcaagagcgttgttgaccaggcc ctcaagtattccccgaatgcttacttcatcatcatctccaacccgatggacgctatgacgttcctgacgctcaaggacacgaagct cccgcgcaaccgcatcctcggccagggcggcatgctcgacagcagccgtttccgttatttcctcgcacaggctctgacgaagg ctggctatccggctacgccggctgacgttgatggcatggtcatcggcggccacagcgacaagacgatggttccgctcgtcagc tatgcaacgctgcgcggcatccctgtaacgcagctcctgagcaaggaagcactcgacgacgttgtcgctcagacgaaggtcg gcggcgctacgctgacgaagctcctecggcacgtccgcttggattgcaccgggcgctgcagctgctacgatggttgaagccatc gccctcgatgccaagaagctcatcccgtgctgcgtctacctcgaaggcgagtatggcgagaaggacctctgcatcggcgtac cgtgcatcctcggcaagaacggcctcgagaagatcgtcgagatcaagctcgatggcgacgagaaggctaaattcgaagag agcgttcaggctgctcgcaacacgaacgcaaaactcggcgatgccctcaaataa

Amino acid sequence (SEQ ID NO:50)

MKVTVVGAGNVGATVANVLATKKFCSEVVLVDIKEGVPQGKAMDIMQTAHMLNFDTTVTG

VTALPNDPEGYAPTAGSDVVVVTSGMPRKPGMSREDLIGVNAKIVKSVVDQALKYSPNAY

FIISNPMDAMTFLTLKDTKLPRNRILGQGGMLDSSRFRYFLAQALTKAGYPATPADVDGM

VIGGHSDKTMVPLVSYATLRGIPVTQLLSKEALDDVVAQTKVGGATLTKLLGTSAWIAPGA

AAATMVEAIALDAKKLIPCCVYLEGEYGEKDLCIGVPCILGKNGLEKIVEIKLDGDEKAKFEE

SVQAARNTNAKLGDALK

Nucleotide sequence (SEQ ID NO:51) atgagcaaattgaacgaccaggcattggccctgcatagagaacaccacggcaagatcgagatgcacagcaaggtccccct ccagaaggcgaaggacctgacgctggcctactegccgggcgtcgctgcgccgtgcttggagattcagaaggactacaacaa gatctatgactacaccaacaagggcaacacggtcgccgtcgtgacgaacggcagcgctgtactcggcctcggcaacatcgg cgctggcgccggcctgccggtcatggagggcaagtccatcctgttcaagggcttcgcaggcgtcgactccgtccccatctgcct cgacacgcaggacgtcgatgagattgtccgcgccgtcgagctcatggcgccgacattcggcggcatcaacctcgaggacat caaggcaccgcagtgctitgacatcgagaagcgcctgcagaaactcgatatcccggtcttccacgacgaccagcacggcac ggccatcgtcgtcgtcteggccctcatcaacgccttcaagctcacgggccgcaagttcgaggagtcgaagttcgtcctcaacgg cgcaggtgccgctggccaggccatcacgcacctcatttacagcatgggcggccgcaacatcatcctctgcgaccgcatgggt gccatctacgaaggccgcaaggaagacatgaacccctacaaggacgccatcgccaaaatcacgaacccgcagcatgag gcgggccagctcaaagacgtcatcaaggacgccgacgtcttcatcggtgtctccgtagccggtgcagtcacccaggacatgg tccgctccatgaagaaggacccgatcgtcatgggcatggccaacccgacgccggaaatcatgccggatgaggcctacgctg ccggtgcccgcatcgtctgcacgggccgcagcgactacccgaatcaggtcaacaacctgctggccttcccgggcatcttccgc ggcgctctcgacgtccgcgcgaaaaagatcaacgaagagatgaagatggctgccgccaaggccatcgccgacctcatcga cgagagcgaactcgatgagcagcacgtcatcacgagcccgttcgacccgcgcgtcgcaccgcacgtcgccgcagccgtag cagatgccgccatcaagactggcgtcgcccgcatcaccgacatcacgcccgacgaggtagccgagcacacccgccagctc ctcgccgccgagcacgccagcgaggcctga

Amino acid sequence (SEQ ID NO:52)

MSKLNDQALALHREHHGKIEMHSKVPLQKAKDLTLAYSPGVAAPCLEIQKDYNKIYDYTNK

GNTVAVVTNGSAVLGLGNIGAGAGLPVMEGKSILFKGFAGVDSVPICLDTQDVDEIVRAVE

LMAPTFGGINLEDIKAPQCFDIEKRLQKLDIPVFHDDQHGTAIVVVSALINAFKLTGRKFEES

KFVLNGAGAAGQAITHLIYSMGGRNIILCDRMGAIYEGRKEDMNPYKDAIAKITNPQHEAG

QLKDVIKDADVFIGVSVAGAVTQDMVRSMKKDPIVMGMANPTPEIMPDEAYAAGARIVCT

GRSDYPNQVNNLLAFPGIFRGALDVRAKKINEEMKMAAAKAIADLIDESELDEQHVITSPFD

PRVAPHVAAAVADAAIKTGVARITDITPDEVAEHTRQLLAAEHASEA

Nucleotide sequence (SEQ ID NO:53) ttgcgagaactcgacgcaaaacaaatcacggaaaccgttgcacagctgtgcaaggaggcggcttattacctgccgaaagat gtctatgagggcctcaagaagggccgcgagacggagaagtccccggttggccaggctgtactcgaccagattatcaagaat gcggaaatcgcacgcgatgaggatcgcccgtactgccaggataccggcatgacgatcgtcttcctcgaggtaggccaggac ctccacatcgtcggcggcgacctcgaagaggcagtcaacgacggtatcgccaagggctacacggaaggctacctgagaaa atcggtcgttgcagagccaatcttcaaccgcgtcaacacccagaacaacacgccgggcgtcatctacacgaagatcgttccg ggcgacaagctcaagatcacggttgagccgaagggcttcggttccgagaacaagggcggcatcaagatgctcgtaccggct gacggccttgagggcgtcaagaaggctgtcatggagatcatcctgcatgccagcatgaacccgtgcccgccgatggtcgtcg gcatcggtatcggcggcacgatggaccgcgccgctgtcatgagcaagattgccctgacgcgttcgatcgactcgcataaccc gatgccagaatatgcgaaactcgaagacgatctcctcgagctcatcaatgaaacgggtattggaccgcagctcggcggcac gacgtcctgcctcggtgtcaacatcgagtggggcccgacgcacatcgccggcctgccggtcgctgtgacgatctgctgccatg catgccgtcatgcaaagcgcgttctttga

Amino acid sequence (SEQ ID NO:54)

MRELDAKQITETVAQLCKEAAYYLPKDVYEGLKKGRETEKSPVGQAVLDQIIKNAEIARDE

DRPYCQDTGMTIVFLEVGQDLHIVGGDLEEAVNDGIAKGYTEGYLRKSVVAEPIFNRVNTQ

NNTPGVIYTKIVPGDKLKITVEPKGFGSENKGGIKMLYPADGLEGVKKAVMEIILHASMNPC

PPMVVGIGIGGTMDRAAVMSKIALTRSIDSHNPMPEYAKLEDDLLELINETGIGPQLGGTTS

CLGVNIEWGPTHIAGLPVAVTICCHACRHAKRVL

Nucleotide sequence (SEQ ID NO:55) atggcagaacctattcgcatccataccccgttcacggaagaagattcccacaagctcaagatcggcgacagcgttctcatcac gggcgagatctacgctgcacgcgatgctgcgcacaagaagatgtgcgaggcactcgctaaaggcgagaagctgccgatcg actggcacaacaagatggtctattacctcggaccgactccggcaaaaccgggtgatccgatcggctcctgcggcccgacgac ttctggccgcatggatgcctacacgccgacgatgctcgagcagggcatcaagggcatgatcggcaagggctcccgttcgaag gaagtcgtcgattccatgaagaagaacggcgttacgtatttcgctgctgteggcggtgccgcagcgctcatcgcgaagtccgtc aagaagtacgaagttctcgcttacccagaactcggcccggaggcacttgcccgcctgaccgttgaggatttcccagctattgttg tcatcgactgcgaaggcaataacctttacgatgtcaaccaggagaagtatcgtaccctgaagggttactga

Amino acid sequence (SEQ ID NO:58)

MAEPIRIHTPFTEEDSHKLKIGDSVLITGEIYAARDAAHKKMCEALAKGEKLPIDWHNKMVY

YLGPTPAKPGDPIGSCGPTTSGRMDAYTPTMLEQGIKGMIGKGSRSKEVVDSMKKNGVT

YFAAVGGAAALIAKSVKKYEVLAYPELGPEALARLTVEDFPAIVVIDCEGNNLYDVNQEKYR

TLKGY

Nucleotide sequence (SEQ ID NO:57) atgttccatacaacttittatctgcgccgtetgcactcgttagtcggcctgctggcaatcggcattttcctcttcgagcatatcattacg aatgctcgtgcactcggcggtgctgagtccctcaacggtgetctggccatgatggagctcatcccgcatccgatcttcctcggcct ggagatcttcggtgtcgcactgccgatcctcttccatgccatctacggcatctacatcgcccttcaggcgaagaacaacccggg ccgctacggctacgtccgcaactggcagttcgctctgcagcgctggacggcatggttcctcgtcatcttcctcatctggcatgtgtt ctacctgcgcatcttcacgaaggccatcaacggcacgccgatctcgtatgagctgctgcatacgctcttcacgagcagcccgat cacgacgctgctctacacgatcggcatgttcgcagctatcttccatttctgcaatggtatcacgactttctgcatgacctggggcat cgccaagggcccgcgcatccagaacgtcatcaacgttctctcgatgtgcctctgegcattcctctgccttgtcacgattgcgttcat ggcaagctactttgtcatgtaa

Amino acid sequence (SEQ ID NO:58)

MFHTTFYLRRLHSLVGLLAIGIFLFEHIITNARALGGAESLNGALAMMELIPHPIFLGLEIFGV

ALPILFHAIYGIYIALQAKNNPGRYGYVRNWQFALQRWTAWFLVIFLIWHVFYLRIFTKAING

TPISYELLHTLFTSSPITTLLYTIGMFAAIFHFCNGITTFCMTWGIAKGPRIQNVINVLSMCLC

AFLCLVTIAFMASYFVM

Nucleotide sequence (SEQ ID NO:59) atggctaagaaaccagaaaataagattattgtegtaggcggcggcctctcgggcctcatggctacgctgaagatctgcgaagg cggcggcaaggttgacctcttctcttactgcccggtcaagcgttcccactccctctgtgcacagggcggcatcaacgcctgcatg gacacgaagggtgagcatgactcgatctacgagcatttegatgatacggtctacggcggcgacttcctegetgaccagctcgct gtcaagggcatggtcgaagctgcaccgaagctcatcaagatgttcgaccgcatgggcgtgccgttcacgcgcacggctgaag gtgttetcgacctccgtaacttcggcggccagaagaacaagcgcacggtcttegctggctccacgacgggccagcagctcctc tacgctctcgacgagcaggttcgccgttgggaagtaaagggcggcgtcaagaagtatgagttctgggaattcatcaagatcat caagaacaaagagggcatctgccgcggtatcgtcgcgcagaacatgaactccaatgagatcgtctcgttcccggctgacgttg tcatcctcgcaacgggcggccetggccaggtatacggccgctgcacggcttcgacgatctgcaacggttcggctgtttccgctgt ttaccagcagggcgctgagctcggcaacccggagttcctccagatccatccgacggctatcccgggttccgacaagaaccgc ctgatgtccgaggcttgccgcggtgagggcggccgcgtctgggtitaccgcaagaacccgcagacgggcgaaaaagagcg ctggtacttcctcgaggatatgtacccggcatacggcaacctcgtaccgcgtgacgttgcatcgcgtgccatctacaaggtcgtc gtccacatgggcctcggcatgcacaacccgaaccgcgtctacctcgacctctcgcacatcccggctgattacctcgagcgcaa gctcggcggcatccttgagatgtacagcgacttcatgggccaggatccgcgcaaggtcccgatggagatcttcccgtcgatcc actactcgatgggcggcatctgggtcgatcgcgagcatcacacgaacatcccgggcctcctcgcttccggcgagtgcgattac cagtaccacggcgcaaaccgcctcggtgcaaactcgctgctgtcggcaacgtactcgggcacgatttctggcccagagtccct gcgcctcgcacgcagcggcaagctcggctctgccctgacggcagaagagctcgaggctgcccgccaggagtgcgtcgcag agttcgacaagatccgcaacatgaacggcacggagaatgcgcataagctccatcatgagctcggcgacatcatgtacaagt acgtctccatcgagcgcgacaacaacggcctcaaagaatgcgtcaaggaactcaaggaaatcctcaagcgctgggacaac atcggcgttacggaccacggcacttgggcaaaccaggaagcgatgttegtccgccagctgcgcaacatgatcatctatgcgat ggccatcacgcagtccgctctgcagcgtgacgagagccgcggtgctcatgcgaagatcgtcctgaagtccgattacgataag atggacgaccagctcaaggaagccctcacgaagaagtacggcaagttccacttcgacgctgagacgggccgtggcacgac ggatgacggcaacgacgacctcgtattcttcgagcgcaacgataagaagttcatgcgcacgaccatcgttaccttcgaccagg agaaggaagagccggtcgtttcctaccgtgaattcgagcactctctcatcaagccgcgtctgcgcaactatgccgtagctaaga aagagtaa

Amino acid sequence (SEQ ID NO:60)

MAKKPENKIIVVGGGLSGLMATLKICEGGGKVDLFSYCPVKRSHSLCAQGGINACMDTKG

EHDSIYEHFDDTVYGGDFLADQLAVKGMVEAAPKLIKMFDRMGVPFTRTAEGVLDLRNFG

GQKNKRTVFAGSTTGQQLLYALDEQVRRWEVKGGVKKYEFWEFIKIIKNKEGICRGIVAQN

MNSNEIVSFPADVVILATGGPGQVYGRCTASTICNGSAVSAVYQQGAELGNPEFLQIHPTA

IPGSDKNRLMSEACRGEGGRVWVYRKNPQTGEKERWYFLEDMYPAYGNLVPRDVASRA

IYKVVVHMGLGMHNPNRVYLDLSHIPADYLERKLGGILEMYSDFMGQDPRKVPMEIFPSIH

YSMGGIWVDREHHTNIPGLLASGECDYQYHGANRLGANSLLSATYSGTISGPESLRLARS

GKLGSALTAEELEAARQECVAEFDKIRNMNGTENAHKLHHELGDIMYKYVSIERDNNGLK

ECVKELKEILKRWDNIGVTDHGTWANQEAMFVRQLRNMIIYAMAITQSALQRDESRGAHA

KIVLKSDYDKMDDQLKEALTKKYGKFHFDAETGRGTTDDGNDDLVFFERNDKKFMRTTIV

TFDQEKEEPVVSYREFEHSLIKPRLRNYAVAKKE

Nucleotide sequence (SEQ ID NO:61) atggcagaacagaaaaaagtcagaatcatcgtcgagcgccaggacggcccgaaagagaagccgtacaaccaggagttc gagatcgactatcgtccgggcctcaacatcgttgctgccctgatggaaatccagaagaacccggtaacggtcgacggcaaga aagtcccgccagtgacgtgggaatgcaactgcctcgagaaagtctgcggcgcctgcatgatggtcatcaacggcaaggctcg ccaggcttgctgcacgctcgttgatacgctcaagcagccaatccacctgcagccggcccgcacgttcccggtcatccgcgacc tgctcatcgaccgctccgtcatgttcgagagcctcaagcgcatccacggctgggtcgaagtcgacggcacgtgggaggtcaa ggatgctccgatccagaacccgtacacggcacagacggcctacgagatctcgcactgcatgacctgcggctgctgcctcgag gcctgcccgaacgtcggcccgcagtccgacttcatcggaccggctccgacggtacaggcttaccttttcaacctccatccgctc ggaaagttcgacgctccgaagcgcctgaacgcactgatggagaagggcggcatcacgagctgcggcaacagccagaact gtgtcgaagcttgcccgaagaacatcaagctgacgacgtatctcgcacagctcaaccgcgatgtcaacaagcaggccctga

Amino acid sequence (SEQ ID NO:62)

MAEQKKVRIIVERQDGPKEKPYNGQEFEIDYRPGLNIVAALMEIQKNPVTVDGKKVPPVTWE

CNCLEKVCGACMMVINGKARQACCTLVDTLKQPIHLQPARTFPVIRDLLIDRSVMFESLKRI

HGWVEVDGTWEVKDAPIQNPYTAQTAYEISHCMTCGCCLEACPNVGPQSDFIGPAPTVQ

AYLFNLHPLGKFDAPKRLNALMEKGGITSCGNSQNCVEACPKNIKLTTYLAQLNRDVNKQ

ALKNIFNH

Nucleotide sequence (SEQ ID NO:63) atggcgactatcaagctggagattgtctcaccggataaagtggtctacgagaatgacatcagcatgctgatcgtccgctcgacg ggcggtgagctcggcatcctgccgcaccatgccccgctcgtcgcgggtetcgtgccgcatgccatgcgcatccgcctcggcgc agaccgcgatgagcagctcatcgcggttgcgggcggcttcatggaagtcacgccggagaagatcacggtcctcgcgacggc tgctgagcagccaatcgacattgacatcaaccgcgcgaaggaggccatggcccgcgccaaggcccgcatcgccgccttcc atcagggcacgcctgagggcaaggacgtcgatatcgaccgcgccgaactcgcactgcgccgctcgagtgcgcgtctgcgcg cactcggctcgcaattcgaagaataa

Amino acid sequence (SEQ ID NO:64)

MATIKLEIVSPDKVVYENDISMLIVRSTGGELGILPHHAPLVAGLVPHAMRIRLGADRDEGLI

AVAGGFMEVTPEKITVLATAAEQPIDIDINRAKEAMARAKARIAAFHQGTPEGKDVDIDRAE

LALRRSSARLRALGSQFEE

Nucleotide sequence (SEQ ID NO:65) ttggcaaaaggtaaagtcgtacaggtcatcggacctgtcgtagatattgaattcccggcgggcgagctgccggcaatcctcaat gccgtcaccatcaagggcaagacgagcattgacatcgacctcgtcgtcgaggtcatgcagcatcttggcgacagcgtcacgc gctgcatcgccatgagctcgacggacggtctgacgcgcggcatggaagcagtcgacacgggcaacccgatcatggtcccg gttggcacggagtgcctcggccgcgtcttcaacgtactcggtcagacggttgaccacaacccggctcctgtcggcaacaagg agtcctggccgatccatcgcccggctccgaagttcgacgagcaggagacgagcgcgcaggtcctcgagacgggcatcaag gtcgtcgacctcatcgctccgtactccaagggcggcaagacgggcctcttcggcggcgcaggcgtcggcaagacggtcctca tcatggagctcatccacaacatcgcgacggagcacggcggttactccgtcttegccggcgtcggcgagcgcacccgtgaggg caacgacctctggggcgagatgactgagtcgggcgtcatcgacaagacggcactcgtctacggccagatgaacgagccgc caggagcacgtatgcgcgtcgccctgacgggcctgacgatggcagagtacttccgcgatgtccagcatcaggacgtgctgct cttcatcgacaacatcttccgcttcatccaggctggttetgaggttteggcactgctcggccgcatgccgtcggccgtcggttatca gccgacgctgtccacggatatcggtgetctgcaggagcgcatcacctcgacgaagaatggttccatcacgtcggttcaggcag tctatgtcccggccgatgacctgacggacccggcaccggctggtacgttcacgcacctcgatgccacgacggtcctctcgcgtc agatcgccgagctcggcatctacccggccgtcgatccgctcgattcgacgagccgcatcctcaacgccgaagtcctcggcga ggagcattacgaagttgcccgcggtgtccaggccgtgctccagaagtacaaggagctccaggacatcatcgccatcctcggc atggaagagctctccgatgaggataagctgactgtctcgcgtgcgcgcaagatccagcgctttetetegcagcccttcttegtcg cagaggtgttcacgggttegccgggcaagtacgtgccgctcaaggagacggtacgcggcttcaaggagatcctcgagggca agtacgatgacctgccggagaatgccttctacatggtcggcacgatcgatgaggcagtggagaaagcacggaagatcaaa gaagaggagggataa

Amino acid sequence (SEQ ID NO:68)

MAKGKVVQVIGPVVDIEFPAGELPAILNAVTIKGKTSIDIDLVVEVMQHLGDSVTRCIAMSST

DGLTRGMEAVDTGNPIMVPVGTECLGRVFNVLGQTVDHNPAPVGNKESWPIHRPAPKFD

EQETSAQVLETGIKVVDLIAPYSKGGKTGLFGGAGVGKTVLIMELIHNIATEHGGYSVFAGV

GERTREGNDLWGEMTESGVIDKTALVYGQMNEPPGARMRVALTGLTMAEYFRDVQHQD

VLLFIDNIFRFIQAGSEVSALLGRMPSAVGYQPTLSTDIGALQERITSTKNGSITSVQAVYVP

ADDLTDPAPAGTFTHLDATTVLSRQIAELGIYPAVDPLDSTSRILNAEVLGEEHYEVARGVQ

AVLQKYKELQDIIAILGMEELSDEDKLTVSRARKIQRFLSQPFFVAEVFTGSPGKYVPLKET

VRGFKEILEGKYDDLPENAFYMVGTIDEAVEKARKIKEEEG

Nucleotide sequence (SEQ ID NO:67) ttggctagtttacaggatattcgccatcgcatcaagagcgtaaagagtaccaagcagatcacgagtgccatgaacatggtcgct acgagccgtctgcgccatgccaaagaggctgcaaccgcgaaccgtccctatgcacagaaggtcagcgaggtcgtccacgc catcgccaagaatgcaggcatggacttctcgcacccactgctcgagaagcacgaggatggcaggaagctcgtcttcctgatc acctcggacaagggattggcaggtgcgtattcgtcgaatgcctgcaaggcggcagagaccctcatcgagaaagcggacgat acggacttcgtcatcgtcggccgcaagggcgtgggccacttcaagacccgcggccacaaggtcatcaaggagttcatcggc atcagcgagcacccgtcttctgaggcggcgcgggacatcgctctcgagctcatccagctctacaagacgggcgagtaccgcg aggtcgacatggtctacacgaagttcgtcteggccatcagctgcgagccgaaatcgggggcgctgetccegttegccccgetg aaggcagaggaccaggacgacctgaacgtcgagtacatctatgagccagatgccgctacggtgctcggtttcatgctgccgc agtatctcttcacggtcgtttatgcagcgcttctgcagtcggcagccagcgagctctcctcgcgcatgaacgcgatgagcaacg cgacggacaacgcagaagacctcatggataaactcaatctgcattacaacaaggtacgtcaggctggcattacccgtgagat cactgagattgtcggcggcgccgaagcccttaagtga

Amino acid sequence (SEQ ID NO:68)

MASLQDIRHRIKSVKSTKQITSAMNMVATSRLRHAKEAATANRPYAQKVSEVVHAIAKNAG

MDFSHPLLEKHEDGRKLVFLITSDKGLAGAYSSNACKAAETLIEKADDTDFVIVGRKGVGH

FKTRGHKVIKEFIGISEHPSSEAARDIALELIQLYKTGEYREVDMVYTKFVSAISCEPKSGAL

LPFAPLKAEDQDDLNVEYIYEPDAATVLGFMLPQYLFTVVYAALLQSAASELSSRMNAMSN

ATDNAEDLMDKLNLHYNKVRQAGITREITEIVGGAEALK

Nucleotide sequence (SEQ ID NO:69) atgaaaatgaatccggaagaaataacggccatcatcaaggaccagatcaagaattacgatgtggacctcaatgttgatgatgt tggttccgttatcgagatcggtgacggcatcgcacacatccatggcctcgacaaggctatggcgggcgagctgctcgatttegg caatgatatttatggtctggtcctgaaccttgagcaggacaacgtcggtgccgttatcttaggcggcgagacgaaaatcaaaga gggctcgcaggtcaagcgcacgggccgcatcatgcaggttcctgtcggtgaggccatgatcggccgcgtcgtcgatgccetc ggccgtccaatcgacggcaagggcaagatcgagacgacggagacgcgtccggtcgagtacccggcaccgggcatcgca gaccgcaagccggtcaaggagccgctgcagacgggcatcaaggccatcgacgccctcgtaccgatcggccgcggccagc gcgagctcatcatcggtgaccgcggcatcggcaagacggccatcgccatcgacacgatcctcaaccagcacgaccagaac tgcatctgcgtctacgtcgccatcggccagaaggcctcgacggtcgcgcgcgtcgtcaagacgctcgaagagcgcggcgcc atggactacacgatcgtcgtcgctgctacggctgctgacagctcgccgctgcagtacctcgcaccgtatgccggtgtcgctatgg ctgagcacttcatgtatcagggcaaggcctgcctctgcgtctacgatgacctcacgaagcacgcagctgcttaccgcgccatgt ccctgctgctccgcagaccgccaggacgtgaagcatatccgggcgatgtcttctacttgcattcccgcctgctcgagcgcgcag cgaagctcaacgatgagctcggcggcggctccatcacggctectgccgatcatcgagacgcaggccggcgacctctcggcct acatcccgacgaacgtcatctccatcacggacggccagatcatgctcgagacggactccttctattetggtatccgcccggcca tcaacgtcggcctctccgtatcgcgtgteggcggctcggctcagatcaaggccatgaagcaggtagcaggtaccctgcgcctc gacctcgcgcagtaccgcgagctcgcagcgttctcgcagttcgcctcggacctcgacaaggagacgaaggcacagctcgac cgcggtatccgcatggtcgagacgctgaagcagccgcagtacagcccgctgctcgtccaggaacaggtcatggtcatctaca cggccgccaagggctatcttgttgatatcccggtcgagaaggtcgtcgagttccagacggacttcctgaagttcatgcgcacgc agcatccggaagtcgcacagaagatcattgaccagaagaaactcgatgatgctctggagacggagctcaagaacgcgatc gtggagttcaaggaaactgtaccgtataaaatggcgtaa

Amino acid sequence (SEQ ID NO:70)

MKMNPEEITAIIKDQIKNYDVDLNVDDVGSVIEIGDGIAHIHGLDKAMAGELLDFGNDIYGLV

LNLEQDNVGAVILGGETKIKEGSQVKRTGRIMQVPVGEAMIGRVVDALGRPIDGKGKIETT

ETRPVEYPAPGIADRKPVKEPLQTGIKAIDALVPIGRGQRELIGDRGIGKTAIAIDTILNQHD

QNCICVYVAIGQKASTVARVVKTLEERGAMDYTIVVAATAADSSPLQYLAPYAGVAMAEHF

MYQGKACLCVYDDLTKHAAAYRAMSLLLRRPPGREAYPGDVFYLHSRLLERAAKLNDEL

GGGSITALPIIETQAGDLSAYIPTNVISITDGQIMLETDSFYSGIRPAINVGLSVSRVGGSAQI

KAMKQVAGTLRLDLAQYRELAAFSQFASDLDKETKAQLDRGIRMVETLKQPQYSPLLVQE

QVMVIYTAAKGYLVDIPVEKVVEFQTDFLKFMRTQHPEVAQKIIDQKKLDDALETELKNAIV

EFKETVPYKMA

Nucleotide sequence (SEQ ID NO:71) atgctaaacttacagcttgtacggaaatacgccaaggcaatcttcgagattgcgcaggaagaggaaaagctcgtggagtatg gcgatgaactcaaggctgcgcgcgagggcatcgagtccgtgccgcaggcgatggagttcttctccaatccgcaggttgatccg aagcagaagaaggagctcctgcagaaatgcttcaagaaagagctctc:gaagaacgtgtaccatttcctgctgctgctggtcga caagcaccgcttcgtgctgttcccggcaatagtggatgagtaccgcgtgctctcgaatgaagccaggggcatcctgatcgcgg acgtgacgacggtcgcgcctgcctcgaagaagcagcagaaggccatcgcagacaaattggaacagataacgggcaaga aagtggagctccgcctccacgaggacaagtcccttatcggcggcgtcgtcgtcaagatcggtgaccgccgcatcgatggcag tgtcgctggccgtctcgagacgatgaagagaaaattactggctaacgagtga

Amino acid sequence (SEQ ID NO:72)

MLNLQLVRKYAKAIFEIAQEEEKLVEYGDELKAAREGIESVPQAMEFFSNPQVDPKQKKEL

LQKCFKKELSKNVYHFLLLLVDKHRFVLFPAIVDEYRVLSNEARGILIADVTTVAPASKKQQ

KAIADKLEQITGKKVELRLHEDKSLIGGVVVKIGDRRIDGSVAGRLETMKRKLLANE

Nucleotide sequence (SEQ ID NO:73) ttgatagatatcaatgccacattgatcgctcagatcttgaacttcttgatcttggctggtctccttcgcgctgttgcctataaaccggtc gtgcggatgctcaaagctcgtcaggaccgcatccaggaaagcctcgacaaggcggatgcagatgctgaggaagcggaca agctcctggctgagtacaaggcaaaacttgcggaggcgaacgtcaaggcggagaacatcgtcctgatggccgagaagcgt gcaagtgaggagcgcgaggcaaagcgcgctgaagtcaagcgcgagattgaacagatgcgcaaggcagcaaaggctga gatcgaccgtgagcgcgagcatgcggtccagcagctgcgcaccgagatgattacgctgtccatggcagccgccggtaagat cgttgctaagaacatggacaagtccgagaacgaagcgctgatctcggatttcgtcaaggaactcgacaaggacaagattggt gatctgccatgctaa

Amino acid sequence (SEQ ID NO:74)

MIDINATLIAQILNFLILAGLLRAVAYKPVVRMLKARQDRIQESLDKADADAEEADKLLAEYK

AKLAEANVKAENIVLMAEKRASEEREAKRAEVKREIEQMRKAAKAEIDREREHAVQQLRTE

MITLSMAAAGKIVAKNMDKSENEALISDFVKELDKDKIGDLPC

Nucleotide sequence (SEQ ID NO:75) atggaaaacgcaatcatggtcgcagcagctctcgtaggtgcaggtctttgcatgggtttggctgcagtcggcgctggcctcggtg atggtcttgtcacgagccgctttatcgaaggtatcacgcgtcagccggaagcacagagcaagctcttcacgaatacgctgatct ccgtcggcctcatcgagtccatggcaatcatcgcaacggtcgttgccctgatcatgctctatgcgaacccgctcatcaaataa

Amino acid sequence (SEQ ID NO:76)

MENAIMVAAALVGAGLCMGLAAVGAGLGDGLVTSRFIEGITRQPEAQSKLFTNTLISVGLIE

SMAIIATVVALIMLYANPLIK atgcatgaaattggtgttcgcgaagtagtgcatttcgccgggttgacattcaactgggagaccctttgcatgacttggctcacgatg gcgatcgtcatcctgatctcatggctggcaacgcggaacctcaagatgattccgacgggctggcagaatgtggtggagatcct cgtctcgtggctcgacacgcaggtgagctccatgatgggcaagcggggactgttcctggcgccgttcatcatgtcgctgttcatgt tcctgctgacgtcaaactggctgggactcatcccgacgttgtcttcgccgacgaatgacttgaacaccaccttggggctggcgct gctcgtcgtcgtactggtacacgtactgggtgtccacatgaagggcggtcattatatcgcgcatttcttcaagccgacgccggtatt tgtcatcatcaacgcgatcgaagagattgccaagccaatcacgctgtcgttccgtctattcggcaacatcctagcaggtgagatc ttgatcatcatcctgctcaagctgatgccaatctggatgccgatcccgtcagtcatctggctggcattcagtatctttgtcggcggag tccaggcgttcatcttcacgatgctgtcgatggcttaccttgcgaatgcagtcaaggaagatgaagaagagtcgtga

Amino acid sequence (SEQ ID NO:78)

MHEIGVREVVHFAGLTFNWETLCMTWLTMAIVILISWLATRNLKMIPTGWQNVVEILVSWL

DTQVSSMMGKRGLFLAPFIMSLFMFLLTSNWLGLIPTLSSPTNDLNTTLGLALLVVVLVHVL

GVHMKGGHYIAHFFKPTPVFVIINAIEEIAKPITLSFRLFGNILAGEILHILLKLMPIWMPIPSVI

WLAFSIFVGGVQAFIFTMLSMAYLANAVKEDEEES

Nucleotide sequence (SEQ ID NO:79) atgaaacagattttatcggtcttcatgaagcgtctcgcgattgccettgggcttgcggcgctgatgatcggcagccttctgctegeg agaggagaagggcagctcatcggcgcactcttcctcggctatttegeggcgctggtatttgtctggaacatggcctggegcctct ggcgcctgacgtacatgcagagtggcggcaagaggcagatgctctggggcatggtgctccggatgctcgtgetettcctegtcc tgctcgtcgcggtgacgatctccgtaccggtattcctegtcacggcgctcggttttetegtetgctatggactcgccctgttcctgetg atccacatgaacctcggtaaaaaataa

Amino acid sequence (SEQ ID NO:80)

MKQILSVFMKRLAIALGLAALMIGSLLLARGEGQLIGALFLGYFAALVFVWNMAWRLWRLT

YMQSGGKRQMLWGMVLRMLVLFLVLLVAVTISVPVFLVTALGFLVCYGLALFLLIHMNLGK

K

Nucleotide sequence (SEQ ID NO:95) atggacgagaaaaacaaggacacgacgcatgagatgctgcgcacgggcctgcgccaggccatcaaggctttegctgtcttg agtggcgtcggcatctacctcgccgtcttegteggcatctgtetgttectcgggaatctggcggacacgtatctcttgggcggcgg ctatgcaggcaagctcacgggcatcctcgtcggcttccccggcgccttctacaccctgttccgtcagctcaagcagaacgggat tgtctga

Amino acid sequence (SEQ ID NO:96)

MDEKNKDTTHEMLRTGLRQAIKAFAVLSGVGIYLAVFVGICLFLGNLADTYLLGGGYAGKL

TGILVGFPGAFYTLFRQLKQNGIV

Nucleotide sequence (SEQ ID NO:81) gtgaatttacaaatcttagtcttagtcctggcgattgtcctgtttggagttctggcatttaaacagatgagcgctttgatcctggctccg cttgtcacgatctttgttgtcatctgctcgaaactcccaattctggactcgttaaaaaatgcgttcatgcctgcagcgtccgactacgt gacaaagtatttccttgtcttctttgteggcgcactgtttggttctgtttaccagtatactggagccgcagaatccattgccagagcca tcgcaggtctctgccgcggaaagttcgtggcaccgatcatcatgatcatcaccggtcttttgacctttggaggagtcagtggctttg ttgtattctttgttatctatccgatcgctctgaacttatttaaagaggcgaaccttacgagaaggcttatcccggctgcaatctctgcc ggatgctggacctggtccatgagcggccctggttctccttccattcagaacgttattgctatggataaccttggtacaccggcaact gccgcatttgttccatctctgatcacaacggttgctatgttittaatgatctttgtatggctggaaatgcgcgcaagaaagtttacaaa aaagggataccgctttattgacaaatctttaaagtatcaattaagtgaagaggagacggcaattgatgaaaacaaagatcttcc tcatgttgccatcgctatccttccgatcattgtaatcctggtactctttaacattgtaaagctgccggtagagacatccgtatttgcag gcgtggctctggctacagttctgatgttcaagagagtcaaaggcatcaacgaatggatcaatgtctttaacaaaggggcatctg attccggtgtcgctatcctgaatactgccattgtcgtaggattcggcggcgttgtgcagaaaacacaggggtttacagatctggtc gctgctctcaaagatatgagcatgccgcctctggtatttgtaatgatcactgtggctgtctatgcaggagcctgcggttccgettceg gcgggatgggcgttgccttcaatgcactgaagtctacctatatcaagatgggaattcctctgccttatgtacataggatttccgcaa ttgccgctggtacattggatacccttcctcaccagggagcgcagatcactctgctcggcatttgtaaaatgacccataaggaagc ctactgggatattgcggttacgcagattatcataccatttatatcctgcggaatctttatcgttttagcttcttttggactataa

Amino acid sequence (SEQ ID NO:82)

MNLQILVLVLAIVLFGVLAFKQMSALILAPLVTIFVVICSKLPILDSLKNAFMPAASDYVTKYFL

VFFVGALFGSVYQYTGAAESIARAIAGLCRGKFVAPIIMIITGLLTFGGVSGFVVFFVIYPIAL

NLFKEANLTRRLIPAAISAGCWTWSMSGPGSPSIQNVIAMDNLGTPATAAFVPSLITTVAMF

LMIFVWLEMRARKFTKKGYRFIDKSLKYQLSEEETAIDENKDLPHVAIAILPIIVILVLFNIVKL

PVETSVFAGVALATVLMFKRVKGINEWINVFNKGASDSGVAILNTAIVVGFGGVVQKTQGF

TDLVAALKDMSMPPLVFVMITVAVCAGACGSASGGMGVAFNALKSTYIKMGIPLPYVHRIS

AIAAGTLDTLPHQGAQITLLGICKMTHKEAYWDIAVTRQIIPFISCGIFIVLASFGL

Nucleotide sequence (SEQ ID NO:83) atgggaaaagttaaaattatcacagcagatcaggctgctgccctggtggaggatcatacaacgatcacaaccagcggatttgt tgccagcggaatgccggaagctctcacaaaagctttggaaaaaagattcaaagaaaccggatcccccaaaaacctgacttt gttttatgctgccgcccagggaaaccgtgacggaagcggcgcggatcattttgcccatgaaggtatgacaaaacgtgtcatag gcggacattggaacatggttcctgcactgggacagatggttctggacaataaaatcgaaggctataatctgcctcagggaaca ctggcacagttataccgtgccatcgcaggtcacaaacccggcgttatcagtcatgtaggattaaatacatttgctgacccacgca ttgagggcggtaaattaaatgacattacaaccgaagatatcgtcgatgtagttgaaatcctgggagaagagaaattattgtaca aatcgttcccgatcaacatcggatttatccgcggtacatatgcagatgaacacggcaacgtaactctgtctcacgaatgtgccac cacagaggtcacaaccatggctcaggccgtaaagaacagcggcggaaaggtcgttgtacaggtagaaaaggtcgtttcag acggcaccttagatccaaaattagtcaagatccctggaatttatgtggatgccgttgtggaagtagaagacatgaaggatcacg aacaatgcgtgggctgtgattatgatggttccatgaccggagacttccgggttccgttaagcagtcttgagtacccgcctctttccg ccaagaagatcattggacgcagagcagccatggaactgacagaaaacacggttgtaaatctaggcattggtattccagagta catctccatggtagccaacgaagaaggcattggagattacatgactctgactgtagaggccggaccaatcggcggtgtacctc agggaggagctaaattcggaggcgctgtcaatgctgaatgtatcctagatcagccgtaccagtttgatttctatgacggcggcg gagttgactatgcattcttaggactcgcacaggcagataaagacggtaatatcaacgtaagcaagttcggtccaaggattgcg ggctgcggcggtttcgtcaatatcacccagaacgcaaaacgctgctacttctgcggaacttttactgcaggaggtctgaagaca tccgtaaaagacgggaaacttatcattgaccaggaaggaaaatcaaacaaattcctggataccgtagaacagatcaccttca gcggtgaatacgcaaataaagtcggccagccggttctctatatcacagaacgtgctgtattcgaactcagaaaggacggcgtc tatctgacagaggttgcccctggtatcgatatccagacacagatcatcgatcatatgggatttgctccaaagatggaaggaacg ccaaagttcatggatgaaagaatcttcaaagatgagctgatgggcctgaagcacgattaa

Amino acid sequence (SEQ ID NO:84)

MGKVKIITADQAAALVEDHTTITTSGFVASGMPEALTKALEKRFKETGSPKNLTLFYAAAQG

NRDGSGADHFAHEGMTKRVIGGHWNMVPALGQMVLDNKIEGYNLPQGTLAQLYRAIAGH

KPGVISHVGLNTFADPRIEGGKLNDITTEDIVDVVEILGEEKLLYKSFPINIGFIRGTYADEHG

NVTLSHECATTEVTTMAQAVKNSGGKVVVQVEKVVSDGTLDPKLVKIPGIYVDAVVEVED

MKDHEQCVGCDYDGSMTGDFRVPLSSLEYPPLSAKKIIGRRAAMELTENTVVNLGIGIPEY

ISMVANEEGIGDYMTLTVEAGPIGGVPQGGAKFGGAVNAECILDQPYQFDFYDGGGVDYA

FLGLAQADKDGNINVSKFGPRIAGCGGFVNITQNAKRCYFCGTFTAGGLKTSVKDGKLIID

QEGKSNKFLDTVEQITFSGEYANKVGQPVLYITERAVFELRKDGVYLTEVAPGIDIQTQIIDH

MGFAPKMEGTPKFMDERIFKDELMGLKHD

Nucleotide sequence (SEQ ID NO:85) atgaacaatttattaatggaagtagaaaacgaagtcgcagttgtaacaatcaacagaccaaaatcattaaacgctttaaacagt gaaactttagctgagttagaccagtgctttacagagatttcaggacgcaaggacatcagagtggtgatcctcacaggatcagg cgaaaaatcctttgtagctggtgctgatatctctgaaatggtcaatgcaactcctgcagaaggaagacagatgggtcttttggca aaagaagcatttcttaagttagagacaatgcctcaggtaaccatcgctgccgtcaacggttacgctctgggaggcggatgcga gatctccatggcatgtgatatccgtgtagctgcggaaaacgcaaaattcgcacagccagaaacaggacttggaattcttccgg gattcggcggaacacagcgtctctcccgtttagtaggaaaaggacgcgcaaaggaattgatctttacatgtgaccagatcgatg ccgaagaagcttacagaattggtcttgcaaacaaagtagtgcctcaggcggagctgatcgattactgtaagaagatggctgca aagatcatgtccaaaggaagctacgcaatttcccttgcaaaagaagcgatcaacacaggaatggacacagacttaagcagc ggtcttacattagaagctgacttattcggacttgcattctccactgctgacaaaaaagagggtatgacagcattccttgaaaaacg taaagctgatttaaaagatttctag

Amino acid sequence (SEQ ID NO:86)

MNNLLMEVENEVAVVTINRPKSLNALNSETLAELDQCFTEISGRKDIRVVILTGSGEKSFVA

GADISEMVNATPAEGRQMGLLAKEAFLKLETMPQVTIAAVNGYALGGGCEISMACDIRVAA

ENAKFAQPETGLGILPGFGGTQRLSRLVGKGRAKELIFTCDQIDAEEAYRIGLANKVVPQA

ELIDYCKKMAAKIMSKGSYAISLAKEAINTGMDTDLSSGLTLEADLFGLAFSTADKKEGMTA

FLEKRKADLKDF

Nucleotide sequence (SEQ ID NO:87) atgagaattttggtttatttaaaagaaataccgccggaagaagaacgggatctgtaccaggatacagaggggatcaatgaca gtgatcagaatgtcttaatggaggcactgaatctgagggacaaggaaggcggaactgtgacggtcatggtcatcgggccgtc cacaggagagaagacagcaagggaggcgctgacctggggagttgacaggtcagtcctggttttaaaggatggaaaggcta caggggatatcctggaaagtgcaagagtgctagcaaaagccatagaagcggaaggcacatttgatgtaattttgtgcggaag acaggcgatagatggagatgcggcccatatggcggctatgacggcgtccittttaaatatcccgcttattgccttctccaaaaaa atggagatctcggacggaaagctgtacaactggtgtatgtccaaagatgggacagaacggacagagtgttgtatgccagcac tggtcctctcagtgaaggaagacaacaaacgaaggcaccccaatgtctgtgatattatgtcagcttatgccgggagcactgtga tcccggttataaaaccagagagaaatacaccggagaagatcattagacaggttgggcagtatacgcccggcaaaaaacac aagaagggaatgatgctggccggaaaagatgaacaggaactggcgggacaactccggcagatattaacgaagttcacgg cagcaaaatag

Amino acid sequence (SEQ ID NO:88)

MRILVYLKEIPPEEERDLYQDTEGINDSDQNVLMEALNLRDKEGGTVTVMVIGPSTGEKTA

REALTWGVDRSVLVLKDGKATGDILESARVLAKAIEAEGTFDVILCGRQAIDGDAAHMAAM

TASFLNIPLIAFSKKMEISDGKLYNWCMSKDGTERTECCMPALVLSVKEDNKRRHPNVCDI

MSAYAGSTVIPVIKPERNTPEKIIRQVGQYTPGKKHKKGMMLAGKDEQELAGQLRQILTKF

TAAK

Nucleotide sequence (SEQ ID NO:89) atggaaagagtatcaaagattttgattattggagaaatacaaaatggacagccagccccggtaactctggaattattagggga gggagagaagatagcctcttctctgaacgcaaagcttttactggctgtagcgggcagcggtattcaggagatcttaagtgagctt ttgcagtatcctgtagacaggatcattgcagtggatcatcccaggatggaattggatcaaacggagacccacgccagagttitg gaggccgtgatccgggagcacgagccggatatgattctgggaggagcaacgttgtcaggaaaggtgctgctgccaatgctg gctgcggttcttggaacagaagtggtgacagacgcggctgacctggagattgacaaggaaacagggaaacttctgatcagc aagccggcgtttgacggaaaaagaatgtctatagtatcgatgccaaaggcccacgtacagatcgtttctgtaaagcccgggatt tttgagaaggcctgcaggacggaaagaaaaagaggcggtatcaccatggtggcggctgactggctggaagatatcaaaga gcggaaaaagatgctggagctgatcacagaagacggcaacaagatatctctggaagattcaaagatcatcgcagccggcg gacggggactgaaagggcctgaaggatttgaactccttacacggtttgcaagagaaatcggtgcccaggtgggctgcacaa gaccatgtgtggatgcaggatggacctcgccggagcagcagatcggccagaccggattcacaaccaaaccggatctctatct ggcttttgggatttccggtgcgatccagcatatgaccggagtccgggcaaagaccgtgatcgcagtcaataacaatccaaatg cggcaatttttaattattgcgactatgggatcgtcggggatgcccaaaaaatattgagagaactactaagagaatag

Amino acid sequence (SEQ ID NO:90)

MERVSKILIGEIQNGQPAPVTLELLGEGEKIASSLNAKLLLAVAGSGIQEILSELLQYPVDRII

AVDHPRMELDQTETHARVLEAVIREHEPDMILGGATLSGKVLLPMLAAVLGTEVVTDAADL

EIDKETGKLLISKPAFDGKRMSIVSMPKAHVQIVSVKPGIFEKACRTERKRGGITMVAADWL

EDIKERKKMLELITEDGNKISLEDSKIAAGGRGLKGPEGFELLTRFAREIGAQVGCTRPCV

DAGWTSPEQQIGQTGFTTKPDLYLAFGISGAIQHMTGVRAKTVIAVNNNPNAAIFNYCDYG

IVGDAQKILRELLRE

Nucleotide sequence (SEQ ID NO:91) atgaattttgaattaacagagcagcaggcagccattcaggaaacagcaaggaactttgctcagacagaactgcagccaggt gtgctggagagagatgcaaacagtgagtttccggtagatctttataagaagatgggggatatgggcctgatcggtcttccatatc cgaaagaagtcggaggacagggagccgattatctttcttatgcactggcagtggaagagatctcaaaagtagatgcctctgtg ggtatttcctattctgtttccacctctctgtatggcggaagcattatgaactctgatgcttccgttgagaaaaagaatgaatttctagca ccggtactgtccggacagcatttcggatcctttggactcacagagcccaatgccggatcagacgcaggcggatgtgtcactgtg gctgaaaaagatggggacgaatacatattaaatggtatgaagtgttttaacaccaacggacctttggccgattatacagcggtat atgccctgacagaacctgagaagaaagcaaagggtctttcctgcittgtagtaaaaaaaggaactcctggattttctgtaggca aggtggaggataagatgggaatccgctctgcgcaggtctctgagatgatcctggaaaatgtcagagtacctgcagagaatatg gtcgttccatctggggacggatttaagctggccatgaagactttggatggaggacgcatcggcgttgccgcgcaggggcttggt atcgcggagggcgcatttgagatcgcaaaagaatacttaaagagcagagaacagttcggcaaaccattatataaaaaccag tatcttgcatttaagatggcggaacttgaaatggagatcgacgctgcaagatacatgctttacaaagcggctacagataaacac gagggaagatcttactcaatcccggcagcaaaggcaaaatacctttgtacagaggccgctatgcatgtgacaacagaagca gtacagatgttaggtggaaatgggtatatgaagggttaccatgtagaacgtatgatgagagatgcgaagatcactcagatctat gagggaaccaatgaaatccagaagctcgttgtaagcggagctatcttcagatag

Amino acid sequence (SEQ ID NO:92)

MNFELTEQQAAIQETARNFAQTELQPGVLERDANSEFPVDLYKKMGDMGLIGLPYPKEVG

GQGADYLSYALAVEEISKVDASVGISYSVSTSLYGGSIMNSDASVEKKNEFLAPVLSGQHF

GSFGLTEPNAGSDAGGCVTVAEKDGDEYILNGMKCFNTNGPLADYTAVYALTEPEKKAK

GLSCFVVKKGTPGFSVGKVEDKMGIRSAQVSEMILENVRVPAENMVVPSGDGFKLAMKTL

DGGRIGVAAQGLGIAEGAFEIAKEYLKSREQFGKPLYKNQYLAFKMAELEMEIDAARYMLY

KAATDKHEGRSYSIPAAKAKYLCTEAAMHVTTEAVQMLGGNGYMKGYHVERMMRDAKIT

QIYEGTNEIQKLVVSGAIFR

Nucleotide sequence (SEQ ID NO:93) tttgagagtcgagtggcaaacgggtgagtaacgcgtagacacctgccgtaaagatggggacaacagttcgaaaggactgct aataccgaatgttgtagagtttccgcatgggaatcctactaaaggtggcctctacttgtaagctatcgctttacgatgggtetgcgtc tgattagctagttggtggggtaacggcctaccaaggcgacgatcagtagccggtctgagaggatgaacggccacattggaac tgagacacggtccagactcctacgggaggcagcagtggggaatcttccgcaatgggcgcaagcctgacggagcaacgccg cgtgagtgaagaagggtttcgactcgtaaagctctgttgtcggggacgaatgtggagatggtgaataaccattttcaatgacggt acctgacgaggaagccacggctaactacgtgccagcagccgcggtaatacgtaggtggcgagcgttgtccggaattattggg cgtaaagggagcgcaggcgggaaggtaagtctatcttaaaagtgcggggctcaaccccgtgaggggatggaaactatctttc ttgagtgcaggagaggaaagcggaattcctagtgtagcggtgaaatgcgtagatattaggaggaacaccagtggcgaaggc ggctttctggactgtaactgacgctgaggctcgaaagcgtggggagcgaacaggattagataccctggtagtccacgccgtaa acgatgaatgctaggtgtaggaggtatcgacccctcctgtgccggagttaacgcaataagcattccgcctggggagtacggcc gcaaggctgaaactcagaggaattgacgggggcccgcacaagcggtggagtatgtggtitaattcgacgcaacgcgaaga accttaccagggcttgacattgagtgaaaggactagagatagtcccctctctteggagacacgaaaacaggtggtgcatggct gtcgtcagctcgtgtcgtgagatgttgggttaagtcccgcaacgagcgcaacccctatcctttgttgccagcacgcaatggtggg aactcaaaggagactgccgcggacaacgcggaggaaggcggggatgacgtcaagtcatcatgccccttatgtcctgggcta cacacgtactacaatgggatggacagagagcagcgaagccgcgaggccaagcgaaccccataaaccatctcccagttcg gattgcaggctgcaacccgcctgcatgaagttggaatcgctagtaatcgcaggtcagcatactgcggtgaatacgttcccggg ccttgtacacaccgcccgtcacaccacggaag

Anaerostipes rhamnosivorans — 16S rRNA

Nucleotide sequence (SEQ ID NO:94) tattttggattgaagttttcggatggatctccttaatgactgagtggcggacgggtgagtaacgcgtggggaacctgccctataca gggggataacagctggaaacggctgctaataccgcataagcgcacagaatcgcatgattcagtgtgaaaagccctggcagt ataggatggtcccgcgtctgattagctggttggcggggtaacggcccaccaaggcgacgatcagtagccggcttgagagagt ggacggccacattgggactgagacacggcccaaactcctacgggaggcagcagtggggaatattgcacaatgggggaaa ccctgatgcagcgacgccgcgtgagtgaagaagtatttcggtatgtaaagctctatcagcagggaagaaataagacggtacc tgactaagaagccccggctaactacgtgccagcagccgcggtaatacgtagggggcaagcgttatccggaattactgggtgt aaagggtgcgtaggtggcatgataagtcagaagtgaaagcccggggcttaaccccgggactgcttttgaaactgtaatgctag agtgcaggagaggtaagcggaattcctagtgtagcggtgaaatgcgtagatattaggaggaacaccagtggcgaaggcgg cttactggactgtcactgacactgaggcacgaaagcgtggggagcaaacaggattagataccctggtagtcnacgccgtaaa cgatgaatactaggtgtcggggccgtagaggcttcggtgccgcagcaaacgcagtaagtattccacctggggagtacgttcgc aagaatgaaactcaaaggaattgacggggacccgcacaagcggtggagcatgtggtttaattcgaagcaacgcgaagaac cttacctggtcttgacatccttetgaccggttnnnaaccgaacctttccttcgggacagaagtgacaggtggtgcatggttgtcgtc agctcgtgtcgtgagatgttgggttaagtcccgcaacgagcgcaacccctatctttagtagccagcatataaggtgggcactcta gagagactgccagggataacctggaggaaggtggggacgacgtcaaatcatcatgccccttatggccagggctacacacgt gctacaatggcgtaaacaaagggaagcgaccccgcgagggcaagcaaatcccagaaataacgtctcagttcggattgtagt ctgcaactcgactacatgaagctggaatcgctagtaatcgtgaatcagaatgtcacggtgaatacgttcccgggtcttgtacaca ccgcccgtcacaccatgggagtcagtaacgcccgaagtcagtgacccaaccgcaaggaggaga

Should there be an inconsistency between the sequences disclosed in the description and the sequences disclosed in the sequence listing, the sequences disclosed in the description are preferred. Alternatively, the sequences of the sequence listing may be used.

CLAUSES

1. Bacterium comprising a gene set that allows said bacterium to convert phytate to 3-hydroxypropionate or a salt or ester thereof, for use in preventing and/or treating metabolic syndrome, insulin resistance, insulin resistance-related condition or obesity, wherein the gene set comprises genes encoding the proteins: phytase, major myo-inositol transporter lolT, myo-inositol 2-dehydrogenase, inosose dehydratase, 3D-(3,5/4)-trihydroxycyclohexane-1,2- dione hydrolase, 5-deoxy-glucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2- deoxy-D-gluconate-6 phosphate aldolase, 2-hydroxy-3-oxopropionate reductase, and D-beta- hydroxypropionate permease.

2. Bacterium for use according to clause 1, wherein the bacterium is in combination with a second bacterium comprising a gene set that allows said second bacterium to convert 3-hydroxypropionate or a salt or ester thereof to propionate or a salt or ester thereof, wherein the gene set of said second bacterium comprises genes encoding one or more of the proteins: permease, oxoacid CoA transferase, dehydratase, electron transfer flavoprotein beta subunit, electron transfer flavoprotein alpha subunit, and Acyl dehydrogenase. 3. Composition for use in preventing and/or treating metabolic syndrome, insulin resistance, insulin resistance-related condition or obesity, wherein the composition is obtainable by: a) growing a bacterium as defined in clause 1 and optionally a bacterium as defined in clause 2 in an aqueous medium suitable therefor; b) separating the bacterium as defined in clause 1 and optionally the bacterium as defined in clause 2 from the aqueous medium to thereby obtain the composition. 4, Bacterium for use or composition for use according to any one of the previous clauses, wherein the bacterium defined in clause 1 is a Mitsuokella species, preferably Mitsuokella

Jjalaludinii or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:93 and/or wherein the bacterium defined in clause 2 is an

Anaerostipes species, preferably Anaerostipes rhamnosivorans or relative thereof having a 18S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:94. 5. Bacterium for use or composition for use according to any one of the previous clauses, wherein the bacterium defined in clause 1 is Mitsuokella jalaludinii as deposited with deposit number CBS150836; and/or wherein the bacterium defined in clause 2 is Anaerostipes rhamnosivorans as deposited with deposit number CBS 140182. 6. Bacterium for use or composition for use according to any one of the previous clauses, wherein the bacterium or composition is not comprised in fecal matter. 7. Bacterium for use according to any one of the previous clauses, wherein the use is in preventing and/or treating insulin resistance or insulin resistance-related condition. 8. Bacterium for use according to any one of the previous clauses, wherein the insulin resistance-related condition is chosen from dyslipidemia, (metabolic) Adenylosuccinate lyase deficiency ((M)ASLD) / (metabolic) dysfunction-associated steatohepatitis ((M)ASH), type 2 diabetes mellitus and insulin-resistance in endocrine disease.

9. Bacterium for use according to any one of the previous clauses, wherein the bacterium is a human intestinal isolate bacterium. 10. Bacterium for use according to any one of the previous clauses, wherein the bacterium is comprised in a composition further comprising a physiologically acceptable carrier. 11. Bacterium for use according to clause 10, wherein the composition is a food composition, preferably a dairy product, more preferably a fermented dairy product, such as yogurt or yogurt drink, or the composition is a pharmaceutical composition, preferably in solid dosage form, such as a capsule, a tablet, or a powder. 12. Bacterium for use according to clause 10 or 11, wherein in the composition the bacterium is present in lyophilized or microencapsulated form. 13. Bacterium for use according to any one of the previous clauses, wherein the bacterium is present in an amount within the range of between 10° to 1015 colony forming units (CFU). 14. Bacterium for use according to any one of the previous clauses, wherein the bacterium is administered separately, sequentially or simultaneously with phytate. 15. Bacterium for use according to any one of the previous clauses for use as a probiotic.

EXPERIMENTAL SUPPORT

EXAMPLE 1 — Identification of microbial phytate metabolism in the human gut and its relation with host health

This Example shows that Misuokelia jalaludinii or another bacterium comprising the identified phytate degradation pathway of Misuokella jalaludinii is able to convert phytate into the antimicrobial 3-hydroxypropionate. The Example also shows the synergy of M. jalaludinii with A. rhamnosivorans in phytate breakdown to beneficial SCFAs (i.e. propionate, acetate, succinate). This also supports that the beneficial effects of dietary phytate on host health may derive from the modulation of the microbiome.

Methods

Phytate degradation by fecal microbiome using stable isotope labeling. Fresh stools were collected from a healthy donor of whom informed consent was obtained following Good

Clinical Practice. The inventors have complied with all relevant ethical regulations for work with human participants. Fresh stool samples from donor A were collected in falcon tubes and quickly brought to an anaerobic chamber to prepare fecal suspension for inoculation. 0.2 ml of fecal suspension was added into 10ml bicarbonate buffered medium containing either 10mM non-labelled phytate or ['*Cs]phytate as sole energy and carbon source. ['*Cs]phytate was synthesized and purified. Samples of [3Cs]phytate enrichments were taken at several time points during a first few days after inoculation. The supernatants of these samples were used for **C-NMR analysis to monitor substrate consumption and end metabolite production. [’3Cs]phytate was synthesized and purified. The first none-labeled phytate enrichments were subsequently transferred to a fresh medium with none labelled phytate as a sole substrate to further enrich for phytate-degrading microbes. At the 3™ transfer, phytate degradation capacity and metabolite production were assessed by HPLC analysis on the bacterial supernatant over 5 days while the pellets were harvested for gDNA extraction and followed by 16S rRNA sequencing analysis to determine changes of the microbial composition during phytate incubation. Stool of donor A was used to extract gDNA and inositol phosphates to further determine the microbial composition by 16S rRNA sequencing analysis and inositol phosphate profiles by 1D- and 2D-NMR analyses (see below for detailed protocol). 1D- and 2D-NMR measurements. All chemicals were used without further purification unless specified. Deuterated solutions (deuterium oxide (D20), sodium deuteroxide (NaOD) and deuterium chloride (DCI)) were obtained from Eurisotop, perchloric acid (HCIOs) from

Supelco, potassium hydroxide (KOH) from Carl Roth, ammonia solution from Sigma Aldrich, tetramethyl phosphonium bromide (TMPBr) from Alfa Aesar, titanium oxide particles (Titanosphere 5 um) from GL Sciences.

For NMR measurements and NMR data analysis, TopSpin 3.5 was used. For formatting, the processed spectra were loaded into MestreNova 10.0 and exported into Adobe Illustrator where lines tracing accumulation of metabolites in stacked spectra were manually added.

Measurements were conducted on a Bruker AV-Ill spectrometer (Bruker Biospin,

Rheinstetten, Germany) operating at 600 MHz for '*H and 151 MHz for **C nuclei equipped with a cryo-QCI probe. The pulse sequence for BIRD-{'H,**C}HMQC is based on the hmaqcbiph pulse program from Bruker. Measurement parameters are adapted depending on sample composition. Typically, HMQC measurements of lyophilized bacterial culture samples were recorded with TD(**C) = 512, 64 scans, spectral width (**C) limited to 50 — 90 ppm.

HMQC measurements of cecal and plasma extracts were recorded with 128 scans, and P1 pulses determined for every single sample, and otherwise identical parameters. For the measurement of *C-NMR spectra of bacterial culture samples TD = 131072, 2048 scans,

and a spectral width of 220-20 ppm were used. All samples were recorded at 310 K. BIRD- {'H,*C}HMQC-NMR spectra were processed without digital water suppression with manual phasing and automatic baseline correction. "*C-NMR spectra were processed with

Sl = 16384, manual phasing and segment-wise automatic baseline correction. Quantification of NMR data were conducted as follows: For cecal extracts InsPs were quantified against a known concentration of tetramethylphosphonium bromide (TMPBr). A standard curve for

InsPs against TMPBr was recorded earlier. For other InsP species, the standard curve for

InsPs was used as an approximation as there are no fully **C-labeled standards available. As the signals of the 2-positions are the sharpest and best resolved (due to the reduced coupling to the neighboring CH groups), the 2-position signals were used for quantification.

For the analysis of metabolites produced in bacterial cultures, capped NMR tubes were roughly sterilized by rubbing with 70 % ethanol and radiation with UV light for 20 min in an aseptic laminar flow hood. Thawn aliquots of bacterial culture samples were centrifuged (5 min, 5000 g, 4 °C) and 500 pL of the supernatant were transferred under aseptic conditions into a sterilized NMR tube and 55 pL of D>O (from a previously unopened bottle which was kept under aseptic conditions) were added for locking during NMR measurements.

Samples were kept at 4 °C until the measurement of !3C-NMR spectra on the same day.

NMR samples which contained multiple InsP species according to the **C-NMR were lyophilized, redissolved in D0, and lyophilized again. Finally, the samples are taken up in 500 pL of D2O and pH adjusted to 6.0 with NaOD and DCI and submitted for recording HMQC and HMQC-CLIP-COSY spectra.

Microbiome profiling analysis. DNA from using from 1ml bacterial culture of fecal phytate enrichments using a repeated bead-beating protocol. For the enrichments, 16S V3V4 amplicon sequences were parsed using a vsearch (v2.15.2) based pipeline. Paired end reads were merged, with max differences set to 100 and allowing for staggered overlap. ASVs were inferred from reads with lower than 1.5 expected error rate using the cluster unoise with centroids algorithm with a minsize of 4, after which chimeras were removed using the uchime3 denovo method. For each sample, ASV abundances were determined by mapping the merged reads against the ASV sequences with identical matches sequence set using the usearch_global algorithm with a 0.97 distance cut off. Taxonomy was assigned using R (V4.0.5) and the dada2 assign taxonomy function using the silva (v132) reference database.

Human cohort study. The HELIUS study is a population-based multi-ethnic prospective cohort study, based in Amsterdam, The Netherlands. Baseline data collection took place between 2011 and 2015 among the six largest ethnic groups in Amsterdam (those of Turkish,

Moroccan, African Surinamese, South-Asian Surinamese Ghanaian and Dutch origin). People in these groups who were aged 18-70 were randomly, stratified by ethnicity, recruited from the municipal registry. Data collection consisted of a questionnaire and a physical examination including the collection of biological samples. Fecal samples were collected from participants. Microbiome data from the HELIUS study was processed. ASV variants with an average abundance of more than 0.1% were selected as representatives. Sequences were placed phylogenetically placed in the tree from the Living tree project (LTP_06_2022) using

MAFFT (V7.310) and Fastree (V2.1.11). The tree was subset to all members of the

Selenomonadales order. Ordination of the microbiome was performed by principal coordinate analysis of the Bray-Curtis dissimilarity. Enterotypes were defined by pam-clustering of the

Jensen-Shannon Distance and were labelled by their major representative clade. Association of the ASVs with the different principal coordinates was determined by calculating the weighted average scores using wascores from the vegan (V2.6.4) package. Differences in prevalence were tested with a chi-square test. Data were visualized using ggplot2. The

HELIUS study complies with all relevant ethical regulations, is in accordance with the

Declaration of Helsinki (6, 7! revisions), and is approved by the Academic Medical Center (AMC) Medical Ethics Committee. All participants provided written informed consent.

Isolation of prevalent Mitsuokella strain. Stool sample of donor A was suspended in anaerobic PBS buffer in an anaerobic tent to make a serial dilution of fecal slurry from 107 to 105. An amount of 200 pl of these dilutions were smeared on a screening agar medium containing phytate as a sole energy and carbon source. The screening medium was prepared by saturating 20mM phytate with magnesium chloride (SIGMA) to produce milky agar plates.

The agar plates were subsequently incubated in an anaerobic jar filled with N2/CO2 at 37°C up to 5 days. Colonies surrounded with clear zones as indication of phytate degradation activities were picked up and streaked on new agar medium to confirm the degradation activity. This streaking was repeated a several times before being inoculated in a liquid medium containing phytate as a sole energy and carbon source. The identity of the isolate was determined via 16S rRNA sequencing at Macrogen, and a draft genome of the

Mitsuokella isolate was sequenced by Illumina NovaSeq 6000 S4 PE150 XP and assembled using Genome de novo assembly pipeline at Eurofins.

Phylogeny of phytases. A phytase phylogenetic tree was constructed from amino acid sequences of phytases and phosphatases from all hosts ranging from mammals to bacterial species that were retrieved from the NCBI database. This included previously reported phytase and phosphatase amino acid sequences from all hosts, E. coli phytase, Akkermansia phytase and Mitsuokella phytase. All amino acid sequences were aligned using the Clustal_X programme. A phylogenetic tree was constructed using the neighbour-joining algorithm by the

MEGA 7 with 1000 bootstraps to obtain confidence levels for the branches.

Bacterial culturing. Mitsuokella jalaludinii DSM 138117 was obtained from DSMZ culture collection and Anaerostipes rhamnosivorans 1y-27 was isolated previously and is available as

DSM262417. These two bacteria were routinely maintained in a modified YCFA medium supplemented with myo-inositol (SIGMA) for A. rhamnosivorans or phytate (SIGMA) for M.

Jalaludinii.

The growth experiments were performed in duplicate in 20 ml bicarbonate-buffered medium supplemented with 20 mM phytate filled with N2/CO:2 (80:20, v/v) gas in the head phase. Phytate and inositol were filter sterilized as stock solutions of 0.2 M and 0.5 M. respectively. The condition in which the bacteria were added to 20 ml bicarbonate-buffered medium without substrate was used as control. The growth was monitored via metabolite formation by HPLC and optical density measurement by a spectrophotometer at a wavelength of 600 nm.

Monoculture and coculture studies of phytate degradation. The coculture study was performed in a bicarbonate buffered medium supplemented with phytate as sole energy and carbon source. Monoculture of M. jalaludinii or coculture of M. jalaludinii and A. rhamnosivorans were inoculated with 10 mM phytate. Bacterial supernatants were collected from both conditions at several time points for substrate consumption and metabolite production by HPLC. To identify the intermediates of phytate degradation by the monoculture and the coculture, the bacteria were inoculated with 5 mM [**Cs] phytate and bacterial supernatants were collected during the growth for NMR measurements. M. jalaludinii

DSM13811" and A. rhamnosivorans 1y-2" were pre-cultured in YCFA medium supplemented with 20 mM phytate or 20 mM myo-inositol respectively. These precultures were added with 2.5 % to the media of the test conditions.

To investigate the synergy between M. jalaludinii and A. rhamnosivorans, the bacteria were grown in monoculture and coculture in a medium containing 10 mM, 20 mM and 40 mM phytate or 10 mM, 20 mM or 40 mM myo-inositol in 96 well plate incubated in an anaerobic tent for growth monitoring for 48 h. At the end of the growth, the bacterial supernatants were collected to analyze the substrate consumption and metabolite production. The experiment was performed in biological triplicate.

To study the growth rate of M. jalaludinii in phytate and myo-inositol; the bacteria were inoculated in YCFA medium supplemented with either 10 mM or 40 mM phytate or 10 mM or 40 mM myo-inositol. The experiment was performed in 96 well plate which was incubated at 37 °C in a plate reader in the anaerobic chamber to monitor the OD600 every 30 min for 24 h.

To study the capacity of A. rhamnosivorans to use 3-hydroxypropionate, the bacterium was incubated in a bicarbonate buffered medium containing 10mM 3-hydroxypropionate or 15mM glucose or both. The cultures were collected during 48 h for OD600 and end metabolite measurements. The experiment was performed in biological duplicate. To study the influence of 3-hydroxypropionate on the growth on myo-inositol, A. rhamnosivorans was grown in 20mM myo-inositol supplemented with either 0 mM, 10 mM, 20 mM, 30 mM, 40 mM, or 50 mM of 3-hydroxypropionate, and the growth was monitored by OD800 measurement every 30 minutes in a plate reader placed in an anaerobic tent. The experiment was performed in biological triplicate.

Analytical methods

Phytate, myo-inositol, succinate, 3-hydroxypropionate and other short-chain fatty acids and alcohols were quantified on a Shimadzu HPLC system equipped with a Shodex sugar

SH1821 6 pm, 8.0 x 300 mm column. The column was kept at 45 °C while running with 0.005 M H2S0. as eluent under a flow of 1 ml/min. The detector was a refractive index detector. Chemicals at HPLC quality were used to prepare the standard curves. All analyses were performed in duplicate.

Transcriptomics. To identify genes involved in phytate degradation by M. jalaludinii

DSM138117, the bacterium was grown in two conditions including a bicarbonate buffered medium supplemented with 20 mM phytate or 20 mM myo-inositol. The experiments were performed in triplicate. The bacteria were harvested after 17 h incubation. Bacterial supernatants were collected to perform HPLC measurement for substrate consumption and metabolite production while the cell pellets were used for RNA extraction. Cells were harvested from 100 ml bacterial cultures by centrifugation at 4700 g for 30 min at 4 °C in 50 ml-pre-cooled sterile falcon tubes. Pellets were washed with 20 ml, 20 mM TE-buffer (pH 7) at 4700 g for 30 min at 4 °C and re-suspended in 150 yl TE buffer. Cell suspension was incubated with Lysozyme at 37 °C for 10 min. Cell lysis and RNase inactivation was performed by addition of a mix containing 4 ul B-mercaptoethanol, 1 pl proteinase-K and 150 pl of Gram-positive lysis solution (Gram positive DNA extraction kit, Masterpure). Lysis was done at 65 °C for 15 min while vortexing every 5 min. After incubation, the mix was quickly cooled on ice for 5 min and proteins were precipitated by adding 175 uL of MPC protein precipitation reagent (Gram positive DNA extraction kit, Masterpure). Debris was removed via centrifugation at 4 °C 10 000 g. The sample was further cleaned and purified via the automated Maxwell LEV simply RNA extraction kit (Promega, Madison, USA), according to manufacturer's instructions. Quality and quantity of the RNA extracts were checked by spectrophotometer DS-11 FX (DeNovix), according to manufacturer's instructions. RNA was collected in RNase free water and stored at -80 °C till further analysis. Depletion of rRNA and sequencing was performed by Novogene (Hong Kong, China) using Illumina high throughput sequencing platform.

To investigate the interaction between M. jalaludinii DSM138117 and A. rhamnosivorans in phytate at molecular levels, M. jalaludinii and A. rhamnosivorans were grown either together or alone in a bicarbonate buffer medium supplemented with 20 mM phytate or 20 mM inositol.

The experiments were performed in triplicate. The bacteria were harvested after 17 h incubation. 1 mL bacterial supernatants were collected to perform HPLC measurement for substrate consumption and metabolite production while the cell pellets were used for quantification of M. jalaludinii and A. rhamnosivorans. QPCR primers for M. jalaludinii were designed to quantify M. jalaludinii in the cocultures and murine microbiome using Primer3 and

Blast based on 16S rRNA sequence of M. jalaludinii DSM138117. The primers were validated using gDNA of M. jalaludinii, which resulted in an 83 bp amplicon. The 16S rRNA gene of M.

Jalaludinii was used to optimize temperature and make standard curves. The qPCR programme was 95 °C for 5 min and 35 cycles consisting of 95 °C for 30 s, 60 °C for 10 s and 72 °C for 40 s; 95 °C for 1 min and 60 °C for 1 min. DNA copies were calculated based on standard curves. qPCR primers for A. rhamnosivorans were used as previously designed and validated. 100 ml bacterial cultures were used for RNA extraction and sequencing as described above. Obtained reads were aligned against reference genomes (BioProject

PRJUNA223472) of M. jalaludinii and A. rhamnosivorans using bowtie2 (V2.5.1). Gene counts were gathered in R (V4.0.5) using feature counts function of the R subread package (V4.3).

Differential expression analysis was performed using DESeq2 (V 1.38.3). For analysis were re-annotated using an available genome from GenBank (BioProject PRINA223472) and re-annotating the genome in Rapid Annotation using Subsystem Technology (RAST).

Animal studies using a stable isotope approach. All animal experiments were done in male C57BI/6J mice (Charles River), which were housed in individually ventilated cages with 2 mice per cage. Mice were kept under constant temperature (19-21 °C); humidity of 40-70 % and a 12h light/dark cycle with free access to food and water. All animal experiments were conducted according to guidelines of the ‘Guide to the Care and Use of Experimental

Animals’ approved by the Ethics Committee on Animal Care and Use in Academisch Medisch

Centrum, The Netherlands. The inventors have complied with all relevant ethical regulations for animal testing and research.

A stable-isotope approach was employed to study in vivo conversion of phytate by

Mitsuokella jalaludinii (MJ) and Anaerostipes rhamnosivorans (AR). Mice were received at the age of 4 weeks and randomized and divided in 2 mice per cage. Acclimatization time was 2 weeks. To reduce the interference of endogenous murine microbiome, mice were treated with antibiotic cocktail of 1 mg ml” ampicillin, 5 mg ml’ streptomycin and 1 mg ml" colistin via oral gavage one time in 1 week prior to the intervention as described previously. To test the in vivo degradation of phytate MJ and AR, 0.2 ml oral administration of 0.1 mg/g body weight phytate or 0.1 mg/g body weight phytate and 10° CFU of MJ or 0.1 mg/g body weight phytate and 10° CFU of MJ and 10° CFU of AR were given to a group of 8 mice every second day for 2 weeks. Bacterial suspension was prepared in 10 % trehalose. In week 3, [!3Cs]phytate-AR-MJ, ['*Cs]phytate-MJ or ['3Cs]phytate challenge were given to a group of 8 mice in corresponding group. To estimate the time preference of in vivo conversion of [’3Cs]phytate, a vial of bacterial suspension of MJ and AR was inoculated in a medium supplemented with 5 mM phytate. Phytate conversion by the bacteria was monitored during 24 h via metabolite measurement by HPLC. The experiment was performed in biological duplicate. Each 4 mice per group were sacrificed after 3 h or 6 h of the *C challenge and cecum contents and blood were collected for targeted metabolomics analyses via NMR,

CE-MS, GC-MS and UHPLC-MS/MS measurements. Detailed methods were described in following sections. Colon samples were collected for quantification of A. rhamnosivorans and

M. jalaludinii by qPCR at 3 h and 6 h time points as described above.

Extraction of InsPs from mouse cecal and plasma samples for metabolomics. The protocol for the extraction of InsPs from cecal samples was adapted from published procedures but scaled to match the higher mass and volume (between 20-120 mg). The cecum content is resuspended in ice-cold 1 M aq. perchloric acid (HCIO., Supelco, 0.1 mL per 1 mg cecum content) in a 5 mL or 15 mL tube by pipetting up and down (using a 1 mL pipette tip with the tip slightly cut off to widen the opening) and vortexing for about 20 s until all major clumps have broken up. The suspension was then incubated for 20 min at 4 °C on a rotary shaker. The sample is then centrifuged (10 min, 21 000 g, 4 °C) in 2 mL tubes and the supernatant transferred into a separate 5 mL or 15 mL tube containing TiO. beads (Titanosphere 5 um, GL Sciences, 0.5 mg of TiO2 per 1 mg original cecum content material), which were already washed with 1 mL Milli-Q® water and 1 mL 1 M perchloric acid. The extract and TiO; beads were mixed by briefly vortexing and on a rotary shaker for 20 min at 4 °C. After centrifugation (10 min, 18 000 g, 4 °C) in fresh 2 mL tubes the supernatant was discarded (note: for transferring the supernatant without disturbing the TiO; beads a 2 HL

Eppendorf tip attached to the tip of a 1 mL tip was used with slow pipetting) and the beads united in a single 1.5 mL tube by resuspending in 1 mL HCIO: in total. After vortexing the suspension was again centrifuged (10 min, 18 000 g, 4 °C) and the supernatant discarded. To eluate InsPs from the TiO. beads, the beads were incubated with 375 pL of 10 % ammonia solution for 5 min at room temperature on a rotary shaker. After centrifugation (IKA miniG, 6000 rpm, 1 min) the supernatant was collected in a separate tube. The elution step is repeated once more and the eluates are combined. The combined eluates are filtered through a 0.2 pm syringe filter (Sartorius Minisart RC4) which was subsequently rinsed with 150 pL of

Milli-Q® water. The filtrate was collected in a new 1.5 mL tube and lyophilized. To reduce the water content for NMR analysis the lyophilized eluates were redissolved in 500 HL DO and lyophilized again. The lyophilized samples were taken up in 500 uL D;O and defined volumes of NaOD and DCI were used to adjust the pH to 7.0. Afterwards, 2.86 uL of a TMPBr stock solution (20 mM in DO) were added for quantification and submitted for NMR measurement.

The extractions of InsPs from plasma samples were performed based on the procedures of TIO: purification method. Briefly, 80-100 uL of plasma was thawed on ice and an equal amount of perchloric aid (2 M, 4 °C) was added. The sample was rotated for 30 min at 4 °C and then centrifuged (15.000 g, 10 min, 4 °C). Transfer the supernatant to pre-washed TiO. beads (5 mg per sample, 5020-75000 GL Sciences) and incubate at 4 °C with rotation for 20 minutes. After that, the suspension was centrifuged (3.500 g, 1 min, 4 °C) and the supernatant was discarded. Wash the unbinding compounds with 0.5 mL perchloric acid (1 M) twice. For elution, NH4OH (200 pL, 3 % [v/v]) was used. The elution step was repeated and the eluents were combined. The combined eluents were centrifuged (17.000 g, 1 min, 4°C) to remove any insoluble residues. For subsequent CE-ESI-MS analysis, the supernatant was completely dried under vacuum evaporation (60 °C) and dissolved into 20 pL of ultrapure water before measurement.

Extraction of myo-inositol from plasma samples for metabolomics. The extractions of inositol from plasma samples were performed. Briefly, plasma samples were thawed and vortexed before transferring 50 pL of sample to 250 yL of acetonitrile containing 1% of formic acid for protein precipitation. After centrifuging, the supernatants were transferred into a

HPLC vial for the UHPLC-MS analysis.

CE-ESI-QQQ analysis of [Ce] InsPs in plasma samples. Known amounts of isotopic standards (2 uM [1302] 5-InsP-) were spiked into samples for quantitation of ['3Cs] PP-InsPs and [20:23] InsPs (2 uM) were spiked into samples for quantitation of [Ce] InsPs. For plasma samples, 2 UM [1302] 5-InsP; and 2 uM [302] InsPs were spiked. For cecum samples, the samples were diluted 20-fold, then 4 uM [1302] 5-InsP7 and 20 uM [13012] InsPs were spiked. A

CE-ESI-QQQ system is used for the measurement. Set MS source parameters and MRM transitions as shown in table. The injection for each sample is 30 nL. “MS Source Parameters

Gas Temperature 15°C

Gas Flow 11 L/min

Nebulizer 8 psi

Sheath Gas Temperature 175 °C

Sheath Gas Flow 8 L/min

Capillary Voltage -2000 V

Nozzle Voltage 2000 V

High Pressure RF (lon Funnel Parameters) 70V

Low Pressure RF (lon Funnel Parameters) 40V “MRM transitions ~~

Molecular Precurs Produ dwell Fragmentor Collision Cell ~~ Polarity name or lon ct lon (V) Energy Accelerato (V) r Voltage

[3Ce]InsPz 345 ~~ 247 50 166 21 4 Negativ e [3Cs]InsP3 424.9 326.8 50 166 17 4 Negativ e [*Ce] InsPs 252 4249 50 166 5 1 Negativ e [Ce] InsPs 292 504.9 50 166 9 3 Negativ e [**Ce] InsPs 331.9 486.9 50 166 13 4 Negativ e

[012] 340.9 4949 50 166 17 4 Negativ

InsPs e [Ce] InsP; 371.9 3229 50 166 9 3 Negativ e ['®0;] InsP; 370.9 319.9 50 166 9 3 Negativ e [3Ce]InsPs 411.9 362.8 50 166 9 1 Negativ e 3C-Myo-Inositol measurement in plasma samples. Plasma ['*Cs]myo inositol was quantified using UHPLC-MS/MS. Analysis was performed on a UHPLC (Agilent 1290 infinity

II) coupled to a Q-TOF (Agilent 8546). Chromatographic separation was achieved using gradient elution on an UHPLC Acquity BEH Amide column (1.7 pm, 2.1 mm x 150 mm) at 30 °C at a flow rate of 0.4 ml/min. Mobile phase consisted of 0.04 % NH4OH (mobile phase A) and 100 % acetonitrile (mobile phase B). Setting of instrument parameters and gradient elution as shown in table. The elution started with 13 % mobile phase A, increased to 17 % mobile phase A between 0 min and 18 min then to 19 % mobile phase A between 16 min to 19 min. Between 19 min to 21 min, mobile phase A was increased to 30 % then held for 2 min. Stock solution of myo-inositol (2 mg/mL) was prepared in ultrapure water, then was diluted in 87 % acetonitrile (starting mobile phase condition for analysis) to obtain five calibration levels (0.1 pg/mL, 0.5 pg/mL, 1 pg/mL, 5 ug/mL, 10 pg/mL) for quantification of myo-inositol in plasma. Each calibration levels have three replicates.

Cecum SCFA measurement. SCFA concentration and *C-enrichment in cecal sample were analyzed. Briefly, samples were thawed, diluted in 500 pL PBS and spiked with 50 pL of (0.5 mg/mL) 2-ethyl butyric acid as internal standard. After adding 10 pL of HCI (12M), samples were homogenized, and centrifuged (20 min, 15000 x g, 4 °C). The supernatant was transferred to a glass vial with a spatula tip of solid NaCl. SCFAs were extracted in 2 mL diethylether. For SCFA derivatization, an amount of 500 pL of diethyl ether was derivatized with 50 pL N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) at room temperature overnight. Mass spectrometry analysis was performed using an Agilent 5975C series gas chromatography/mass spectrometry (GC-MS) (Agilent Technologies, Santa Clara,

USA) equipped with a ZB-1 column (Phenomenex, Torrance, USA). The mass isotopologue spectra of ([M-57]*) fragment of the derivatives of acetate (m/z 117-1119, mg-my), propionate (m/z 131-134, mg-m3) and butyrate (m/z 173-149, mo-ms) were monitored. The standard curve were prepared in a range of 10 uM to 10 mM for acetate, 3 uM to 3 mM for propionate and butyrate. These ranges covered all measured points.

Caco-2 cell testing. To investigate the effects of microbial metabolites on barrier integrity,

TEER (Transepithelial electrical resistance) experiments in Caco-2 cells were performed. As propionate is the major metabolite from phytate break-down by the coculture, effect of propionate on barrier integrity was accessed in Caco-2 cell with transwell setting. To produce bacterial supernatants for Caco-2 cell work, a coculture of M. jalaludinii and A. rhamnosivorans was grown in YCFA containing 20mM phytate. The pH of the cultures was monitored every day and adjusted to neutral pH after addition of substrates. The pH adjustment and substrate addition were conducted every day for 5 days. Bacterial supernatants were collected at all time points for HPLC measurement.

At 80 % of confluence of the Caco-2 cell culture, cells were treated with Trypsin-EDTA and seeded apically at 5x10* cells/well onto a 20-well, 12 mm ThinCert™ with 0.4 um pore membrane, TC-treated (Coming, CLS3460). Growth media were renewed every 2 days with

DMEM containing 10 % fetal bovine serum (FBS), 1 % Penicillin-Streptomycin and 1 % of non-essential amino acids. Caco-2 cells were incubated in an incubator maintained in a humidified atmosphere at 37 °C with 5 % CO.. Caco-2 cells were seeded on transwells for 21 days to obtain a monolayer for TEER measurement. TEER analyses were performed at day 7, 14, and 21 in culture. After 21 days, the medium in the apical compartment was replaced with medium containing either 20mM propionate; 10 % M. jalaludinii and A. rhamnosivorans supernatant or 10 % YCFA medium as control. TEER measurement was performed at TO; 4 h; 7 h; 24 h and 30 h. Cells with fresh medium was used as control condition. At the end of the experiment, the supernatant in the apical compartment was collected for HPLC analysis while Caco-2 cells were washed with 300 uL of PBS and collected in 300 pL of Trizol/Tripure®. These cells were then stored at -80°C freezer for RNA extraction and qPCR to quantify the activity of tight junction genes. The experiment was performed in biological triplicate.

In order to assess the influence of propionate and bacterial metabolites on barrier integrity, total RNA was extracted from cells incubated with either water or 20 mM propionate, 10 % bacterial supernatant of the coculture of M. jalaludinii and A. rhamnosivorans, 10% bacterial medium using TriPure reagent according to manufacturer's instruction. Quality and concentration of extracted RNA were determined by Nanodrop. The cDNA was amplified using SensiFAST SYBR Green PCR Kit (Meridian bioscience, USA), following the manufacturer’s instructions. Human tight junction genes (Claudin 1, Occludin, E-cadherin,

Claudin 2 and ZO1) were amplified using specific primers, with expression being normalized to 18S and 36B4 genes. The gPCR programme was 10 minutes at 95°C, 39 cycles consisting of 15 seconds at 95 °C and 30 seconds at 60 °C and melting curves were obtained at between 65 °C to 95 °C with an increment of 0.5 °C every 5 seconds. Fold changes were calculated using 2¢9. The qPCR was performed with technical duplicates.

RESULTS

Fecal phytate metabolism identifies human Mitsuokella spp. as efficient phytate degraders. To gain a better understanding which bacteria are involved in the rapid degradation of phytate, the inventors incubated fresh fecal samples from a healthy donor (A) in a medium supplemented with ['?Cs]phytate as the sole carbon and energy source. The supernatants from [**Cg]phytate enrichments were collected over time and used for the analysis of 'C-labelled components by *C-NMR. In parallel, non-labelled phytate fecal enrichments were repeatedly transferred to fresh phytate media to further enrich for phytate degrading microbes. The inventors observed that the fecal microbiome metabolized ["Cs]phytate within a few hours to [*C;]acetate and [**C3]3-hydroxypropionate, which was subsequently converted to ['3C3]propionate after 24h (Fig. 1a).

To identify the phytate-degrading microbes, genomic DNA was isolated from phytate enrichments after two transfers during which bacteria involved in phytate metabolism were highly enriched and subjected to 16S rRNA gene amplicon sequencing. The inventors observed a microbial community enriched from fecal microbiomes with Ruminococcaceae,

Mitsuokella and Bulyricicoccus as the most abundant taxa (Fig. 1b). At the end of the phytate incubation, the relative abundance of most species decreased, whereas that of Mitsuokella spp. increased in both enrichments up to 10 % of total microbiome, with M. jalaludinii as the most dominant species (Fig. 1b-c). Of note, the relative abundance of Mitsuokella increased gradually during the first 48 h, which was in line with a rapid degradation of phytate within 30 h (Fig. 1c). Overall, these results suggest that M. jalaludinii is involved in phytate degradation in the human gut.

Mitsuokella as prevalent taxon in the human Gl tract and its health relation. To further investigate the prevalence of Mitsuokella in the general population and determine its ecological niche, the inventors analyzed the microbiome of 6039 Amsterdam-located subjects in HELIUS cohort with different ethnicities. The inventors found three amplicon sequence variants (ASV) of Mitsuokella which represented 89 % of all Mitsuokella counts. These sequence variants were highly similar to those belonging to Mitsuokella multacida or

Mitsuokella jalaludinii. A total of 1542 out of 6039 subjects were positive for one of these clades, indicating the high prevalence of Mitsuokella in the general population. All three clades had bimodal distributions with either absence or presence of which relative abundance were between 0.01 to 10 %. Mitsuokella is closely related to known fiber-degrading species, including ruminal Selenomonas spp., one of which has been reported to have an active periplasmic phytase. Mitsuokella spp. were also strongly associated with the Prevotelia

Enterotype, which has been linked with high fiber intake and health status. The prevalence of different clades of Mitsuokelfa spp. varied slightly among the ethnicities but most subjects harbored M. jalaludinii. To verify its functionality, the inventors isolated a dominant

Mitsuokella strain from donor A and found it to grow fast on phytate and its genome sequence to be highly similar (an average nucleotide identity of 97.3 %) to that of the type-strain

M. jalaludinii DSM138117 with greatly identical phytate degradation pathway genes. Hence, this confirms that M. jalaludinii is highly prevalent in human. Of note, M. jalaludinii remained as the most prevalent Mitsuokella species in both genders with higher prevalence in male. It was recently reported that the abundance of fecal Mitsuokella spp. was significantly lower in cardiometabolic patients compared to the healthy population. This prompted the inventors to further study the role of M. jalaludinii in phytate degradation and its contribution to metabolic health.

Complete phytate degradation pathway by Mitsuokella jalaludinii DSM13811" characterized via stable isotope and transcriptomic analyses. The inventors used M. jalaludinii DSM138117 for proof-of-concept experiments and cultured it in a medium containing phytate or myo-inositol as the sole energy and carbon source. M. jalaludinii grew rapidly in phytate with a doubling time of 3.4 h, while the doubling time with myo-inositol was 7 h (Fig. 2a). The metabolite production was similar between both conditions. Based on the observed stoichiometry of phytate conversion, the inventors propose the net theoretical fermentative equation as: 1 phytate + 6 Hs0 — 1 3-hydroxypropionate + 0.4 lactate + 0.2 succinate + 0.2 acetate + 0.6 CO. + 6 phosphate. Of note, the formation of CO, was not determined due to the pre-existing bicarbonate in the medium but predicted based on carbon and redox recovery.

To unambiguously identify the pathway, its intermediates and all end metabolites of phytate degradation, M. jalaludinii was grown in bicarbonate buffered medium containing either [!3Ce]phytate or [13Cs]myo-inositol as the sole energy and carbon source. As observed by 1D-NMR and 2D-NMR spectroscopy, M. jalaludinii converted ['3Cs]phytate rapidly to various metabolites with [13C:]3-hydroxypropionate, [**Cs]lactate and [’3C:s]succinate as major end metabolites (Fig. 2b). The inventors identified the accumulation of myo-inositol-2-monophosphate (Ins{(2)P) and myo-inositol during the first 7.5 h via 2D-NMR

(Fig. 2c), suggesting that these are intermediates of phytate degradation. The capacity to use myo-inositol was confirmed by the growth of M. jalaludinii and conversion of ['3Ce]myo-inositol to [3C3]3-hydroxypropionate, ['3C:]lactate and [**Ca]succinate. The production of 3-hydroxypropionate from phytate assured our previous hypothesis that Mitsuokella spp. were responsible for the efficient fecal phytate degradation in which 3-hydroxypropionate was detected as intermediate (Fig. 1a).

To further identify genes of M. jalaludinii involved in phytate metabolism, the inventors analyzed transcriptomic profiles of cells grown in either phytate or myo-inositol. The differential expression of the whole transcriptome between two conditions is shown in a volcano plot in which phytate metabolic genes are highlighted. The inventors found the gene for a periplasmic phytase (MJ_0021) constitutively expressed in both conditions (Fig. 2d).

Evolutionary analysis showed that the encoded phytase was only distantly related to other microbial and human phytases, which may imply its unique capacity to readily dephosphorylate phytate to inositol (Fig. 2b-c). The expression of the genes for an inositol transporter (MJ_0380) and a high affinity phosphate transport system PstSCAB (MJ_0656-0658) were 8-fold increased during the growth on phytate as well as the electron transport chain by a succinate dehydrogenase membrane complex (MJ_0311-0313) and ATP synthase (MJ_0861-086%). The inventors also identified induced expression of 2-hydroxy-3-oxopropionate reductase {(MJ_1281) and a 3-hydroxypropionate penmeass (MJ 0911) involved in 3-hydoxypropionaie production and transport, respectively. Genes involved in acetate, lactate and succinate, 3-hydroxypropionate production, glycolysis and

ATP synthase were identified, all of which except a pyruvate carboxylase were expressed constitutively (Fig. 2d). The metabolomic and transcriptomic analyses imply that the faster growth of M. jalaludinii on phytate as compared to myo-inositol may likely be due to the increased activity of the inositol transporter. Based on the NMR and transcriptomic analyses, the entire metabolic phytate degradation pathway was reconstructed. The observation that a monoculture of M. falaludinii mainly produced succinate and 3-hydroxypropionate and not the canonical short chain fatty acids from phytate, suggests that there are metabolic interactions between Mitsuokella with other commensal bacteria in the human colon.

Mechanistic understanding of in vitro synergy between M. jalaludinii and

A. rhamnosivorans in phytate. |t has been shown that supplementation of A. rhamnosivorans in fecal phytate enrichment increased propionate formation. Hence, the inventors investigated the potential synergy between M. jalaludinii and A. rhamnosivorans in phytate degradation. The inventors observed that the cocultures reached higher cell density compared to monocultures of M. jalaludinii independent on phytate concentration (Fig. 6a).

The inventors detected propionate and acetate in the cocultures while 3-hydroxypropionate and lactate were only accumulating in the M. jafaludinii monoculture with presence of succinate in both conditions (Fig. 6b). This indicates a potential synergy between these two bacteria leading to propionate production upon phytate degradation. To gain mechanistic insight into this interaction, the inventors monitored and compared phytate metabolism by monoculture of M. jalaludinii versus coculture of M. jalaludinii and A. rhamnosivorans using both non-labelled and *Ce-isotopomer of phytate. The inventors observed that 3- hydroxypropionate was first produced and subsequently converted to propionate after 8 h in the coculture (Fig. 3b-c), while 3-hydroxypropionate accumulated in the monoculture of M.

Jalajudinnii (Fig. 3a), suggesting a trophic chain involving 3-hydroxypropionate as an intermediate. Interesting, the inventors found that A. rhamnosivorans was indeed able to convert 3-hydroxypropionate to propionate particularly in presence of glucose as carbon source, indicating a co-metabolic conversion (Fig. 7a-c). Of note, glucose consumption was reduced in the presence of 3-hydroxypropionate, suggesting inhibition of the glucose metabolism. This was further supported by a slower growth of A. rhamnosivorans on myo- inositol in the presence of increased 3-hydroxypropionate levels (Fig. 7d}. This 3-hydroxypropionate-mediated inhibition of A. rhamnosivorans metabolism may be so potent that most released inositol from phytate dephosphorylation might be taken up and used by M. jalaludinii. These results imply that the synergy between the two intestinal bacteria was mainly via 3-hydropropionate interspecies transfer. Furthermore, *C-NMR analysis confirmed 3C-labelled propionate, succinate and acetate as end metabolites from ['3Ce]phytate in the coculture (Fig. 3c), with [**Cs]Ins(2)P and [!3Cs]Inositol as intermediates. The commonalities between the monocultures and cocultures indicates the limited influence of A. rhamnosivorans on phytate dephosphorylation by M. jalaludinii (Fig. 3c).

To further investigate the microbial interaction at the molecular level, the inventors assessed the differential expression of phytate degradation pathway genes of M. jalaludinii and myo-inositol degradation pathway genes of A. rhamnosivorans during growth in monocultures compared with cocultures on phytate and myo-inositol using transcriptomic analyses. The results of the metabolic time-course measurements showed high concentrations of 3-hydroxypropionate only in monocultures of M. jalaludinii at the expense of high propionate concentration in the cocultures in both phytate and myo-inositol (Fig. 8a-b).

The inventors found that the number of cells of the two bacteria were similar when grown on phytate while the cell numbers of A. rhamnosivorans were 3-fold higher than that of M.

Jalaludinii with myo-inositol as a carbon source (Fig. 8c-d). A. rhamnosivorans had small effects on the overall transcription profiles of M. jalaludinii grown in phytate in contrast to strong influence on M. jalaludinii transcriptomic profile grown in myo-inositol (Fig. 8e). For M. jalaludinii, the expression of genes involved in phytate dephosphorylation, inositol uptake, inositol fermentation was highly similar between monoculture and coculture in phytate (Fig. 3d) while genes involved in myo-inositol uptake and utilization and 3-hydroxypropionate export (MJ_911) were up to 70-fold decreased in the coculture grown on myo-inositol, indicating reduced uptake and consumption of myo-inositol by M. jafaludinii due to the presence of A. rhamnosivorans. Comparing the whole transcriptome profiles of A. rhamnosivorans between cocultures and monocultures, the inventors identified an entire operon (AR1Y2_1112-1117) involved in 3-hydroxypropionate transport (AR1Y2_1114) and conversion to propionate, which was increased up to 19-fold in coculture versus monocultures (Fig. 3e). This observation confirms the active conversion of 3-hydroxypropionate to propionate by A. rhamnosivorans in coculture, which is in line with the metabolic prediction. In contrast, the expression in A. rhamnosivorans of the inositol uptake gene (AR1Y2_0316) and the inositol utilizing operon (AR1Y2_1104-1107) were decreased around 15-fold in the cocultures, suggesting the reduced use of myo-inositol in the presence of M. jalaludinii.

Based on these results, the inventors reconstructed a model of metabolic interaction between

M. jalaludinii and A. rhamnosivorans for phytate utilization (Fig. 3f and Fig. 9).

Elucidation of in vivo phytate conversion by M. jalaludinii and A. rhamnosivorans.

To interrogate the in vivo synergy between these two species in a mouse model, the inventors administered non-labeled phytate with either no microbes, M. jalaludinii alone or

M. jalaludinii together with A. rhamnosivorans for two weeks before ['*Cs]phytate oral challenge (Fig. 4a). The inventors quantified *C-inositol phosphates by NMR and CE-MS analyses in mouse cecum and plasma as well as the bacteria in mouse colon after 3 h and 6 h oral gavage. The inventors observed that the ['*Cs]phytate level was significantly lower after 3 h and 6 h oral challenge in groups receiving bacteria (Fig. 4b-c), indicating the active conversion of phytate by M. jalaludinii or M. jalaludinii plus A. rhamnosivorans in the murine digestive tract. Mice that received the bacteria (both M. jalaludinii with and without

A. rhamnosivorans) had less than 0.5 nmol of [**Cs]phytate per mg cecal content as opposed to 4 nmol of ['*Cs]InsPs per mg cecal content from mice that did not receive the bacteria after 3 h oral challenge. This is reflected by high levels of M. jalaludinii in mouse colon samples of bacterial treatment groups compared with the phytate-only group (Fig. 4d). Similarly, the level of A. rhamnosivorans was high in mouse colon samples after treatment while completely absent in M. jalaludinii treatment and only phytate groups (Fig. 4e). The difference of ["Ce]InsPs level between the treatment groups and the control group was smaller at 6h after of oral challenge, suggesting the residual mouse microbiome was capable of degrading InsPs but at a slower rate as compared to those with supplemented with M. jalaludinii (Fig. 4c).

Importantly, no ['*Cs]insPs and ['*Cg]-myo-inositol were detected in the mouse plasma at both 3 h and 6 h time points by CE-MS, indicating the microbiome was mainly responsible for dietary phytate consumption. Remarkably, the inventors detected large enrichment of 3C-propionate but not *C-acetate or minor *C-butyrate in mouse cecal samples, indicating the major production of propionate from oral phytate (Fig. 10). However, no significant difference in propionate accumulation was observed between the treatment groups and the control group which reflected the reported rapid absorption of short chain fatty acids by colonocytes. While ['3Ce]InsPs was the most abundant inositol phosphate component in the mouse cecum, smaller amounts (<0.25nmol/mg cecum) of other inositol phosphates (InsPs[30H], Ins(1,2,5,6)P4 and/or its enantiomer Ins(2,3,4,5)P, and InsPs[50H]) were also detected in the cecum samples of the mice (Fig. 4f-h). Of note, InsPs[50H)] level was significantly lower in bacterial treatment groups (Fig. 4h) whereas InsP4 and InsPs[30H] levels were higher in two treatment groups compared to the control group (Fig. 4f-g), implicating multiple phytate degradation pathways in presence and absence of these two administered bacteria. Based on these data, two main microbial phytate degradation routes in mouse cecum were deduced as summarized in Fig. 4i.

Microbial phytate derived metabolites improved barrier integrity via activating tight junction genes in Caco-2 cell model. To further investigate potential health benefits of microbial phytate degradation by M. jalaludinii and A. rhamnosivorans, the inventors examined effects of the SCFA propionate as a major end metabolite from phytate degradation on barrier integrity using a Caco-2 cell model. The inventors incubated 20 mM propionate in 3-week seeded Caco-2 cells on transwell and measured the barrier integrity by transepithelial electrical resistance (TEER) analysis over the course of 30 h and quantified the expression of genes involved in tight junction by qPCR. The inventors observed a significant increase of

TEER upon propionate incubation as compared to control (Fig. 5a). The inventors found that tight junction genes Claudin-1, Claudin-2 and E-cadherin were upregulated in propionate condition which is in line with the TEER measurement (Fig. 5b). To produce the bacterial supernatant that contains similar amounts of propionate for Caco-2 cell test, the inventors added phytate to a coculture of M. jalajudinii and A. rhamnosivorans and adjusted pH back to neutral in the end of fermentation of each addition (Fig. 11). The inventors observed that 10 % supplementation of the bacterial supernatant to the apical compartment improved epithelial barrier integrity (Fig. 5c} and increased activities of tight junction genes Claudin-1 and E- cadherin (Fig. 5d). All in all, these data suggest that metabolites derived from phytate breakdown by M. jalaludinii and A. rhamnosivorans, mainly consisting of propionate, improved the barrier integrity via activating tight junction genes.

EXAMPLE 2 - Dietary supplementation

Beneficial effect. The supplementation of a subject with a bacterium according to the present disclosure, e.g. Mitsuokella jalaludinii and optionally Anaerostipes rhamnosivorans provides a direct or synergistic effect on improved insulin resistance, presumably via additional propionate production.

Treatment. Patients are treated as indicated below, according to the following 4 treatment arms:

Treatment 1: 6 weeks, twice daily empty supplement.

Treatment 2: 6 weeks, twice daily supplement with 108 living cells of a bacterium according to the present disclosure, i.e. Mitsuokella jalaludinii.

Treatment 3: 6 weeks, twice daily supplement with 103 living cells of a bacterium according to the present disclosure, i.e. Mitsuokella jalaludinii and Anaerostipes rhamnosivorans.

Treatment 3: 6 weeks, twice daily supplement with 108 living cells of a bacterium according to the present disclosure, i.e. Mitsuokella jalaludinii and Anaerostipes rhamnosivorans in combination with 25 gram nuts.

No. of Condition Effect Effect Effect Effect patients treatment 1 treatment 2 treatment 3 treatment 4 (patient 1) (patient 2) (patient 3) (patient 4) 4 Insulin No effect Reduction of Reduction of Reduction resistance Insulin Insulin of Insulin resistance with | resistance with | resistance 10%* 12.5%* with 14.5%* * as determined by hyperinsulinemic euglycemic clamp, HOMA(-IR). It is expected that results similar to the putative effects as shown in the table above can be obtained with larger patient cohorts.

EXAMPLE 3 — Use of other host bacteria (1)

Another host bacterium, Escherichia coli is transformed according to standard methods with a gene set according to the present invention and comprising (PTP-like) phytase, major myo-inositol transporter [0IT, myo-inositol 2-dehydrogenase, inosose dehydratase, 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase, 5-deoxy-glucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase, 2-hydroxy- 3-oxopropionate reductase, and D-beta-hydroxypropionate permease.

Preparation of Competent Cells. A single colony of E. coli is transferred into 5 mL of LB broth and incubated overnight at 37°C with shaking. Then, 50 mL of fresh LB broth is inoculated with 1 mL of the overnight culture. The culture is incubated at 37°C with shaking until it reaches an optical density at 800 nm (OD8600) of 0.4-0.6. The culture is then transferred to a pre-chilled centrifuge tube and centrifuged at 4°C for 10 minutes at 3000 x g.

The supernatant is discarded and the cell pellet is resuspended in 20 mL of ice-cold molecular biology-grade water. The, the cell pellet is centrifuged again and resuspended in 2.5 mL of ice-cold 10% glycerol, and transferred to small tubes.

Transformation. 1-5 uL of each plasmid DNA (containing the target genes) is transferred to 50 |L of competent cells on ice, and gently mixed, and then incubated on ice for 30 minutes. The mixture is then transferred to a pre-chilled electroporation cuvette. The cells are electroporated using appropriate settings for E. coli. Immediately, 1 mL of SOC medium is added to the electroporated cells and the mixture is transferred to a sterile tube. The cells are incubated at 37°C with shaking for 1-2 hours.

Plating. The transformed cells are plated onto LB agar plates containing the appropriate antibiotics for selection of successfully transformed cells. The plates are incubated at 37°C overnight.

Analysis. The presence of the target genes is verified by PCR or DNA sequencing, and protein expression is confirmed by performing enzyme assays or Western blotting. It is found that the host bacterium is capable of converting phytate to 3-hydroxypropionate under anaerobic conditions (UHPLC-MS/MS as disclosed herein).

EXAMPLE 4 — Use of other host bacteria (2)

Additionally, Escherichia coli is transformed according to methods as described in Example 3 with a gene set according to the present invention and comprising permease, oxoacid CoA transferase, dehydratase, electron transfer flavoprotein, beta subunit, Electron transfer flavoprotein, alpha subunit, Acyl dehydrogenase, and oxoacid CoA transferase

Itis found that the host bacterium is capable of converting 3-hydroxypropionate to propionate under anaerobic conditions.

P36534NL0O0 Wageningen Universiteit Bacterium comprising phytate-degradation pathway 96 879 DNA PAT source 1..879 mol_type unassigned DNA organism unidentified ttgctttatcatatcctgcacaaaaaaataaatttctctctgctgctggccgtctgtctgatactaataaatgcaccagcca tcgctgcggctgcagttcctgaggaacctgcctggcggctcgatgcggccatcggcagtgacgagccgattcatttccg ccgcgatgcagatcttaaaatcgcgggcggcgggcagccgacaaaagaagtcctcgcccatctgcccgcacttctcg gcgtcccgcccgatatgcctatctgggatattgacctgcggcaggaatcccacggctttctcaatcatgcggccgtgag ctggcatggcccgcagaatgcggcgaatcgcggccttgccgcaacagaagtcgaacaagacgaaacggcccgcct gcaggaggcccttggacaccttgtccaagccctgccgatgggccgctacgatgaagaacatatcaaaacatcttttgc tgaaccagtagagagctggtcaacggaacgcgaactggcgcgcagagccgggctcggctacaagcgctttgccgcg accgatatggaatggccggggcctgcggtcatcgatgacttcgtcgacttttaccgcagcctgccaaagaatcacggc tggctcttcttccactgccaggccggacagggccgtacgacgacgtttatggtactctatgagctgctggaacatccatc cgtcaccgcagatgaggcaattgcgcatcagcgcagcctaggcggtgccgacctttcaagcgggccgcgttatcatg gcctgcagcttttcgcccattatgtcaaagaaaactgtgcgtcaaattttcagcaaacatggagccagtggctggctgc ccgacaaaattcttactaa 292 AA PAT source 1..292 mol_type protein organism unidentified

MLYHILHKKINFSLLLAVCLILINAPAIAAAAVPEEPAWRLDAAIGSDEPIHFRRDADLKIAGGG

QPTKEVLAHLPALLGVPPDMPIWDIDLRQESHGFLNHAAVSWHGPQNAANRGLAATEVEQDE

TARLQEALGHLVQALPMGRYDEEHIKTSFAEPVESWSTERELARRAGLGYKRFAATDMEWPG

PAVIDDFVDFYRSLPKNHGWLFFHCQAGQGRTTTFMVLYELLEHPSVTADEAIAHQRSLGGAD

LSSGPRYHGLQLFAHYVKENCASNFQQTWSQWLAARQNSY 1407 DNA PAT source 1..1407 mol_type unassigned DNA organism unidentified atggcggaatcatctcatcgcaaatacctcaagcgtgtcacagtcgtctcgacgttcggtggcttgctcttcggttatga caccggcgtcatcaacggcgcccttgccttcatggcccgtccggatcagttgaacctgactccggcagtggagggcttc gtggccagtggcctgctcttcggtgcggccatcggttcgttctteggcggccgtctttcggatgctgagggacgccgca agatgctgctttgcctggcagtcatcttcttcttegcagccatcggctgctcgctgtcaccgacggctggcatcctcatcg cctgccgcttcgtcctcggcctggcagtcggtggtgcttcggtcacggtacctgcttacctggcagagatggcaccggc cgacaggcgcggccgcatggtcacccagaatgagctcatgatcgtcacgggccagctgctcgccttcatcctcaacgc tatcctcggcgtcaccttcggtgaggtcggccacatctggcgttacatgctcgcactcgcatccatcccggctgtcgtgct ctggttcggcatgctcgtgatgccggagagcccgcgctggctgctgctgcagggccgtgtcagcgatgcgatgcaggt actcaagaagatccgcgatgagcgcatggccatcgccgagctcaacgagatccaggacagcatcgattcggagaag catctcgacaaggctggttacaaggacctggcaacgccttggatccgccgcatcgtcttcatcggcatgggcgtctcca tctgccagcagatttctggcgtcaactccatcatgtattacggcacgcagatcttgacgcaggccggcttctcgacgga agccgcactgatcggcaacatcgccaacggcacgatctccgttgctgccacaatctttggcatgtggctcatgacgcgt cacggccgtcgtccgctcatcatgacgggccagatcggcacgatggcctgcctctgcgcgatcggcgttctctcgaatc tgcttgccggcaccgagatcctgccgttcgtcgtcctttegctgaccgtcaccttcctgttcttccagcagggtttcetttcc ccggtcacctggctgctgctctcggagctcttccecgctgcgcatccgcggcatgggcatgggctgcgcegtcctctgcct ctggctgacgaacttctgcatcggctcggcettccegtegctgctctactcgttcggccetctcggctacgttcttcatcttcg cggccatcggccttctcggcctcgcettcgtctacaagttcgtgccggagacgcgtggccgcacgctcgagcagatcg agcatgacttccgccatcacggtgagaagagcgttcactgcgaagagaaagcttga 468 AA PAT source 1..468 mol_type protein organism unidentified

MAESSHRKYLKRVTVVSTFGGLLFGYDTGVINGALAFMARPDQLNLTPAVEGFVASGLLFGAA

IGSFFGGRLSDAEGRRKMLLCLAVIFFFAAIGCSLSPTAGILIACRFVLGLAVGGASVTVPAYLA

EMAPADRRGRMVTQNELMIVTGQLLAFILNAILGVTFGEVGHIWRYMLALASIPAVVLWFGML

VMPESPRWLLLQGRVSDAMQVLKKIRDERMAIAELNEIQDSIDSEKHLDKAGYKDLATPWIR

RIVFIGMGVSICQQISGVNSIMYYGTQILTQAGFSTEAALIGNIANGTISVAATIFGMWLMTRH

GRRPLIMTGQIGTMACLCAIGVLSNLLAGTEILPFVVLSLTVTFLFFQQGFLSPVTWLLLSELFPL

RIRGMGMGCAVLCLWLTNFCIGSAFPSLLYSFGLSATFFIFAAIGLLGLAFVYKFVPETRGRTLE

QIEHDFRHHGEKSVHCEEKA 888 DNA PAT source 1..888 mol_type unassigned DNA organism unidentified atggctaatatcaaacttggtatcgctccgattgcttggacgaacgacgacatgccggatctcggcaaagagaatacg tttgaacagtgcgtcagtgagatggcactggctggcttcacgggctgcgagatcggcaacaagtacccgaaagatcc ggctgtcctcaagaaagcactcgaccttcgcggactccagatcgccagcgcatggttcagctcctacctcctcacgcag ccgtacgagcaggtcgagaaggacttcatcaagcactgcgaattcctcaaggccatgggcgcgaagttctgcaacgt cgcagagcagggcacgagcgttcagggcaagctcgacaaggctgtcttccgcgacaagccgcacaacacggaaga gcagtggaagacgctcgctgagggcctcaacaagctcggtgctgtcgccaagaagattggcctgacgatgacgtacc atcatcacatgggcacctgtgtccagacgacggaagagattgaccgcctcatggagatgacggatccagacctcgtct tcctgctctacgatacgggccatctcgtctgctccggtgaggacccgatctacatcctcaagaagtacctgccgcgcatc cgtcacgtacatctcaaggacatccgcatggacatccgcaacaaagtcaaggaagagaacatgagcttcctcgcagg cgtccgcgcaggcatgttcacggtcccgggcgatggcgacttcgacttcggtccggtcttcgacatcatcaatgacagc gactacgatggctggttcatcgtcgaagctgagcaggatccggccaaagccaacccgctcgagtacgcgatcaaagc tcgcaagtacatcaaggaaaaagcacatatctga 295 AA PAT source 1..295 mol_type protein organism unidentified

MANIKLGIAPIAWTNDDMPDLGKENTFEQCVSEMALAGFTGCEIGNKYPKDPAVLKKALDLRG

LQIASAWFSSYLLTQPYEQVEKDFIKHCEFLKAMGAKFCNVAEQGTSVQGKLDKAVFRDKPH

NTEEQWKTLAEGLNKLGAVAKKIGLTMTYHHHMGTCVQTTEEIDRLMEMTDPDLVFLLYDTG

HLVCSGEDPIYILKKYLPRIRHVHLKDIRMDIRNKVKEENMSFLAGVRAGMFTVPGDGDFDFG

PVFDIINDSDYDGWFIVEAEQDPAKANPLEYAIKARKYIKEKAHI 1950 DNA PAT source 1..1950 mol_type unassigned DNA organism unidentified atggctaagacaatcagactcacggtagcacaggctctcgtgaagttcctcaataatcagtatgtagaatttgacggc aaggaagtgccgatgttcgaaggcatcttcggcatcttcggccacggcaatgtcatcggcatcggccaggctctcgaa gaggatccgggccatctgatcatgcgcatgggccgcaatgagcagggcatggcacacgcagcgatgggctttgcca agcagaagcgccgcaagcagatgtacgcctgcacgtcttcegtcggcccgggcgctgccaacatggtcacggcagct gctacggctacggcaaactgcatcccagtcctgttcctgccgggtgacacgtacgccgaccgccagccggatccggta ctccagcagatggagcagacggtaagcctgacgacgacgacgaacgacgccttccgcgctgtctgcaaatactggg accgcgtcacgcgtcctgaaatcctcatgacggcctgcatcaatgcgatgcgcgtcctgacggatccggctgagacgg gtgctgtctgcatcgctctgccgcaggatgtcgaaggcgaggcctgggattacccagattacttcttccagaagcgcgt tcatcacatcgaccgcgtaaaaccgacggagcgcgccattgaagaggctgtcaaggccatcgcgaaggctgagcgc ccgctgatgatcttcggcggcggcgtcaagtattccgaggcagaggctgtcttccagaaattcgctgagaagtacggc atcccgttcggcgagacgcaggccggcaagggcacgattacgtgggagcatgagctcaacatgggcggcgtcggc gagacgggcggccttgcagccaacacgcttgcaaaagatgcagatgtcgtcatcggcgtcggcacgcgatacacgg acttcacgacgtcctctaagtggatcttccagaacccgaacgtccagtacgtcaacatcaacgtctcccgcttccatgcc tacaagctcgatggcatccaggttgtcggcgatgccggcgcagcactcgagatgctcgatgaggccctcggcaagac gggctaccatgtgtcggatgcctatgctgcggacatcaaggcagccaaggaagcctatacgaaggaagtcgagcgt gtcttccacatccagttcggcgacaacttcgtgccggaagtcgacgatgatttcgattacaaggctgcagagaaagcct ataaagaggcagtcggcgagacgctgccgcagacgcgcgtcctcggtctgctcgaagagcacatggatccgaacgg catcatcgtcggtgcatcgggctccctgccgggcgacctgcagcgcgtatggcgtccgaagacggttggcagctacca tgtcgagtacggcttctcctgcatgggttatgaagtcaacgcagcactcggcgtcaagctcgctgagccgcagcgcga agtctatgcgctcgttggcgactacgcttacatgatgctccattcggaactgccgacgtccatcgctgagggcaagaag atcaacgtcatcctgttcgacaacatgcagggcggctgcatcaacaacctcgagatcggccatggccagggcagcta cggcacggagttccgcttccgcaacgagaagacgggccagctcgacggtgcctatgtaccggttgacttcgccatga acgccgcttcctacggctgcaagagctacacggctcataccgaggaagagctcatcgcggccatcgaagatgctaag aagcagaaagtctcgacgctcatcgactgcaaggtcatgccgaagacgatggttcacggctacggtgactggtggcg tgtcggcgtcgcgcaggtctccaagagcaagaagatccacgactgctacgagaatctcatgaagccgcattacgatg cagctcgcaagtattga 649 AA PAT source 1..649 mol_type protein organism unidentified

MAKTIRLTVAQALVKFLNNQYVEFDGKEVPMFEGIFGIFGHGNVIGIGQALEEDPGHLIMRMG

RNEQGMAHAAMGFAKQKRRKQMYACTSSVGPGAANMVTAAATATANCIPVLFLPGDTYADR

QPDPVLQQMEQTVSLTTTTNDAFRAVCKYWDRVTRPEILMTACINAMRVLTDPAETGAVCIAL

PQDVEGEAWDYPDYFFQKRVHHIDRVKPTERAIEEAVKAIAKAERPLMIFGGGVKYSEAEAVF

QKFAEKYGIPFGETQAGKGTITWEHELNMGGVGETGGLAANTLAKDADVVIGVGTRYTDFTT

SSKWIFQNPNVQYVNINVSRFHAYKLDGIQVVGDAGAALEMLDEALGKTGYHVSDAYAADIK

AAKEAYTKEVERVFHIQFGDNFVPEVDDDFDYKAAEKAYKEAVGETLPQTRVLGLLEEHMDPN

GIIVGASGSLPGDLQRVWRPKTVGSYHVEYGFSCMGYEVNAALGVKLAEPQREVYALVGDYA

YMMLHSELPTSIAEGKKINVILFDNMQGGCINNLEIGHGQGSYGTEFRFRNEKTGQLDGAYVP

VDFAMNAASYGCKSYTAHTEEELIAAIEDAKKQKVSTLIDCKVMPKTMVHGYGDWWRVGVA

QVSKSKKIHDCYENLMKPHYDAARKY 798 DNA PAT source 1..798 mol_type unassigned DNA organism unidentified atgagattcggtcgcttaggtcagctcaagcacggctacaatgcaatgacgacgcgcgagagcgatatgctcatgga tatcggttaccaggagatggatgagaacgagatcgtcgagttcgaagatccccttcaggagacggccttcgtcatcac gacgggtgatgtggagatctgctggaatggcaagaaagagctcatgcatcgcgagtcgctgctcgacgagaacccg tactgcctgcacgtgccgcacggcgtcaaggtcgtcgtcaaggccctgaagaaatcggagctcctgatccagaagac gctcaacgaccgcgactttgagccggtcttctaccgtccgaaagatgtccaggctgacgttttcggcggcggcgtatgg cagggcacggcagagcgcacggtccgcacgatcttcgattacgacaatgcgccgtactccaacatggtcaacggcga agtcatcatgacgccgggctgctggacgggctacacgccgcacaatcatccgcagccggaagtctacacctacaaag tcgaccgtccgcagggctttggctgtgcgttcatcggcgacaacgtcttcaagatcgaggacaacacttggtcggaga tctcgggcggctacatgcatccgcagtgcgcagctcctggctacgccatctggtacagctggatgattcgtcatctcga cggcgatccgtggaagaagacgcgcaatgacctgccggagcacacctggctgctcgagccggatgccgattcgaag atctggcagccgcacaagaagtga 265 AA PAT source 1..265 mol_type protein organism unidentified

MRFGRLGQLKHGYNAMTTRESDMLMDIGYQEMDENEIVEFEDPLQETAFVITTGDVEICWNG

KKELMHRESLLDENPYCLHVPHGVKVVVKALKKSELLIQKTLNDRDFEPVFYRPKDVQADVFG

GGVWQGTAERTVRTIFDYDNAPYSNMVNGEVIMTPGCWTGYTPHNHPQPEVYTYKVDRPQG

FGCAFIGDNVFKIEDNTWSEISGGYMHPQCAAPGYAIWYSWMIRHLDGDPWKKTRNDLPEH

TWLLEPDADSKIWQPHKK 1035 DNA PAT source 1..1035 mol_type unassigned DNA organism unidentified atggcactcattagctttgatgaaaacaagaaacgcgatgtcgtcctgattggccgcgtcacgctggatttcaatccga atgaactgaaccgcacgctggacaaggtcaagactttctccatgtacctcggcggttcgccgggaaacatggctgtcg gcatcaacaagttgggcaagaacgtcggtttcatcggctgtgtatctgacgaccagttcggcgacttcgtcctcaattac ttcaatgagcgtggcattgacacgtcccagatgacgcgcgccaagaacggcgagcgcatgggtctgacgttcacgga gatcaagagcccgacggagtcgagcatcctgatgtaccgcgaccaggtcgctgacctcgagattgcgccggaagat gtcgatgagcagtacatcgctgacagcaagatcctgattgtctccggtacggcgctctcgaagagcccgtcgcgtgag gcatgcctgctggctgtccagtatgccaagaaacatggcacgcgcgtcatcttcgatatcgactatcgcccgtacagct ggcgcagcaagaaggacatccagatctactactcgttgcttgcgagcatggccgatgtcatcatcggttcgcgcgatg aggtcaacctcacggaaggtctcgatgaggaggcaacggagccggcagatcacgtcatcgctgagaagtacatcga gcagggtgccaagattgtcatcatcaagcacggcaagaagggctcgatcgcttacacggccgacaagaaggcctac aaggttgagtcgtaccacatcaagctgctgaagtcgttcggcggcggcgatgcgtatggcagcgcctttgtctatggcc tgctcgcaggctggacggtgccgcaggctctgcagcacggcacggcacacgccgctatggtcgtcgcaagccacag ctgctcagatgccatgcagacggtcgagcagattgatgctttcatgcaggaacataaagacgagaaagtcatcacgg aattggattgggaggcagcattatga 344 AA PAT source 1..344 mol_type protein organism unidentified

MALISFDENKKRDVVLIGRVTLDFNPNELNRTLDKVKTFSMYLGGSPGNMAVGINKLGKNVGF

IGCVSDDQFGDFVLNYFNERGIDTSQMTRAKNGERMGLTFTEIKSPTESSILMYRDQVADLEI

APEDVDEQYIADSKILIVSGTALSKSPSREACLLAVQYAKKHGTRVIFDIDYRPYSWRSKKDIQ

IYYSLLASMADVIIGSRDEVNLTEGLDEEATEPADHVIAEKYIEQGAKIVIIKHGKKGSIAYTAD

KKAYKVESYHIKLLKSFGGGDAYGSAFVYGLLAGWTVPQALQHGTAHAAMVVASHSCSDAM

QTVEQIDAFMQEHKDEKVITELDWEAAL 843 DNA PAT source 1..843 mol_type unassigned DNA organism unidentified atgccactcgtacatttgacagacctcataagcaagccagacaacacatatgcaattggcgcgttcaatgtctcggata tggagatggccatgggtgccatcaaggcggcagaagagctccatgctccgctgatcctgcagattgcagaaggccgc ctgcgctactcgcegctcgacctgcttggcccegtgatgatcgcggccgccaagaagtgctcgatgccgacggccgttc atctcgaccacggcagcacgatggagacgatcaagcttgcgctcgacctcggcttcacgtccgtcatgttcgacggttc gaaatatccgctcgatgagaacatcgcccgcacgcaggaagtcgtcaagcttgcgaggagctacggcgctgacgtc gaaggtgagatcggccgcgtcggcggcgcggagggcgactacaagagcgtggatgtcctcgtcacgagcgtcgag gaagccaagcgctttgccgaggaatccggcatcgatgcgatggccgtcgcaatcggaacggcacatggcaactaca aggagaagccgcagctccgcatcgaccgcctcaaggaaatccatgcggccgtcaagacgccgctcgtcctgcacgg cggcacgggcctgacggaagaggatttccggacttgccttgccaacggcatccagaagatcaacatcgccacggcgt cgtacgacgcttcggcagcgaagataaaggaagtcgctgcagcgaacccgcaggcaaagtacttcgatttcagcgat gccatcgtacagggcacctacgagaatgtaaagaaacacatgcacatcttcgggctcgaacagaaggcatga 280

AA PAT source 1..280 mol_type protein organism unidentified

MPLVHLTDLISKPDNTYAIGAFNVSDMEMAMGAIKAAEELHAPLILQIAEGRLRYSPLDLLGPV

MIAAAKKCSMPTAVHLDHGSTMETIKLALDLGFTSVMFDGSKYPLDENIARTQEVVKLARSYG

ADVEGEIGRVGGAEGDYKSVDVLVTSVEEAKRFAEESGIDAMAVAIGTAHGNYKEKPQLRID

RLKEIHAAVKTPLVLHGGTGLTEEDFRTCLANGIQKINIATASYDASAAKIKEVAAANPQAKYF

DFSDAIVQGTYENVKKHMHIFGLEQKA 897 DNA PAT source 1..897 mol_type unassigned DNA organism unidentified atgaagaagattggttttgtaggactgggcatcatgggcaaaccgatggttcgcaatctcttgaaagcaggctttgctg tgactgtctacgatatcgtggaggatgcagtcaaggcactggtagaagagggggcaaagggtgcttcttcagcaaag gaagttgcagcggatcaagacgtcgtcatcacgatggtaccgagtggtccgattgtccgctcgttgctcaagggcgat gacggcatcctggctggtgtcaaggaaggcacggtcatcgtggatatgagctccgtcacgccggtggaatcgaagg aatttgctgaactggcagcagagaagggatgcgcgttcctcgatgcaccggtcagcggcggtgagccgggtgcagtt gcaggttcgctggccattatggtcggcggtgaagaagctgtcctcaatcaggttcgcgatgtctttgaagcgatgggat cttccatcacactggtcggaccgacgggcagcggctcggtgacgaaactggccaatcaggtcatcgtcaacctcaata tcgcagcggtagccgaagcgctcatcctttcgaccaaggccggcgcggatccgaagaaagtctacgaggcaatccgc ggcggtctggctggcagcacggtgctggatgctaaggcaccgatgatgttccgccgcaatttcaaaccgggcggacc gatcaagattaacctcaaggacatcacgaatgtcatggatacggccaagaaactcgacctgccactcgtcatgacgg gggtgctggagcagatcatgcacagcttgaaggcgacgggccatctgatggatgatcacagtggcattgtccagttct atgagaatatttccggtgtcgtagtcaagacgcatgaagagtga 298 AA PAT source 1..298 mol_type protein organism unidentified

MKKIGFVGLGIMGKPMVRNLLKAGFAVTVYDIVEDAVKALVEEGAKGASSAKEVAADQDVVIT

MVPSGPIVRSLLKGDDGILAGVKEGTVIVDMSSVTPVESKEFAELAAEKGCAFLDAPVSGGEP

GAVAGSLAIMVGGEEAVLNQVRDVFEAMGSSITLVGPTGSGSVTKLANQVIVNLNIAAVAEAL

ILSTKAGADPKKVYEAIRGGLAGSTVLDAKAPMMFRRNFKPGGPIKINLKDITNVMDTAKKLD

LPLVMTGVLEQIMHSLKATGHLMDDHSGIVQFYENISGVVVKTHEE 1416 DNA PAT source 1..1416 mol_type unassigned DNA organism unidentified atgggcatcagcatgattgtcttcagcctgatacttttgatgttcttcgcgtatcgtggctattccatcatcttcatcgcacc gattttcgcegtcgtcgccgccatcggcagcggccacgcctccatgccggtctacagtgagatctatatgacgaaagcc gcggagtacatcaagacgtattaccccgtcttcetgctcggcgccgtcttcgccaagatcatggagcagggcgggctc gcggcggccgtggccgacaagatcgtctcggcgctgggccgcgacaaggccattctggccgtactgctcggatgcgg cgtcctgacgtacggcggtctctctgtcttcgtcgtcgcctttgtcatgtacccatttgctgccatcctcttcaagcaggctg atatcccgaagcgtctgttgccggggctgctctggatgggtatcttcacctacagcatggtggccatcccgggcacacc gcagatccagaacatcattccgacgtcgttctttggcacttcgacctggtcggctccggtgctcggcctcatcggtgccg tgctctacttcggactggcctggggctggatcagctatcgccacaagaaactcaaggcaaagggtgagggatacggt caccatgtgctcaatgagccggaggagtcgcgggaggctctgccggactggcgcctgtcctcactgccgctgcttcte gtcatcgtgctgaatctcctgatcagcaatccgttccactgggattgggcgtaccactgggatccggaaagcctcgaca gtttcatcccactgcacctctccctgctcgcgggcggcgtcgacaaggtacaggccatctggtccatcaatgcggctctt atcgtgagctccatcgtcgcggccatcatcggccgcagacggctgagactcaagggcggtctctcaaagcccatcaac acgggagccatcggctcgacgacggccatcctcaacgtagcttcaggctatgcctacggctgtgtcatcgcagccttgc cagccttcacgatcatcaaggaagcattgctcggcctgcacctcggcgacggcccgctgatgtctgccatcgtgacga cgggcatcatgacgggcgtcacgggctcttcctcgggcggcatgacgattgccctcggcatgctcggacaggagtgg ctggcctgggcgcagcagatcggcatgagtgcagatgtcctgcaccgcatcatctgcatggcctctgagtgcatcgac accgtgccgcagtcgggcgcactcgtcacactgctcgccgtctgcggcctgacgcatcgcgagtcgtattacgacgttg tgatcctgacgctcctgaagacgcttgtcgtcttcgcctgcctgggcgtctacctgatgacaggtattgaatga 471

AA PAT source 1..471 mol_type protein organism unidentified

MGISMIVFSLILLMFFAYRGYSIIFIAPIFAVVAAIGSGHASMPVYSEIYMTKAAEYIKTYYPVFLL

GAVFAKIMEQGGLAAAVADKIVSALGRDKAILAVLLGCGVLTYGGLSVFVVAFVMYPFAAILFK

QADIPKRLLPGLLWMGIFTYSMVAIPGTPQIQNIIPTSFFGTSTWSAPVLGLIGAVLYFGLAWG

WISYRHKKLKAKGEGYGHHVLNEPEESREALPDWRLSSLPLLLVIVLNLLISNPFHWDWAYH

WDPESLDSFIPLHLSLLAGGVDKVQAIWSINAALIVSSIVAAIIGRRRLRLKGGLSKPINTGAIG

STTAILNVASGYAYGCVIAALPAFTIIKEALLGLHLGDGPLMSAIVTTGIMTGVTGSSSGGMTIA

LGMLGQEWLAWAQQIGMSADVLHRIICMASECIDTVPQSGALVTLLAVCGLTHRESYYDVVIL

TLLKTLVVFACLGVYLMTGIE 933 DNA PAT source 1..933 mol_type unassigned DNA organism unidentified atgaagggagccgaagggctccagggttccaatcagcaagtgatttggggaggaaataatatgttcaacaagatga agaaacttctttccgtcggtgctgttgtcgcgagtgcggcagtgctgctggcgggctgcggcggtggcagccagcagg cttccagctcttctggcagcgcagcacaggaaatctccggcaagatctcagcgtcgggctcgacggcactcctgccgct cttgaagccggcacaggaagccttccaggacaagtacgataaggtgacggtcaacatcgcaggcggcggttcgttca cgggtatgaaccaggtcgcagagggatcggtccagatcggcaactcggatgtcaacctgccggatgagtacaagga caagggcctcgtcgaccacaaggtcgtcgttgagccgttcgtcttcatcgtcgacaagaacaacaaggtcgacaacat cacgaagcagcaggtcatcgacatcctgacgggcaagatcacgaactggaaggaagtcggcggcgatgaccagcc gatcacgctgatccaccgtgcaaagtcctcgggttcccgtgcgacgatcagcgatgtcgtcctcaagggcgcagccttc acggataacgcagtcatccaggattccaatggtgcagttcgcgccgctatcgccagcacgccgggctccatcggctat gtcgatgcaccgtatgccgatgattccgtcaagatcctgaagttcgatggcgttgagtattctccggagaacatcatcg ccggcaagtatccgatctatggctatggccacatgtacacgaaaggtgagccgactggcgcggtcaaggcattcatc gactacatcctcagcgatgagttccagaacacgcaggtcgagaagctcggcttcatccctgtcaacaagatgaagaa gtaa 310 AA PAT source 1..310 mol_type protein organism unidentified

MKGAEGLQGSNQQVIWGGNNMFNKMKKLLSVGAVVASAAVLLAGCGGGSQQASSSSGSA

AQEISGKISASGSTALLPLLKPAQEAFQDKYDKVTVNIAGGGSFTGMNQVAEGSVQIGNSDV

NLPDEYKDKGLVDHKVVVEPFVFIVDKNNKVDNITKQQVIDILTGKITNWKEVGGDDQPITLI

HRAKSSGSRATISDVVLKGAAFTDNAVIQDSNGAVRAAIASTPGSIGYVDAPYADDSVKILKF

DGVEYSPENIIAGKYPIYGYGHMYTKGEPTGAVKAFIDYILSDEFQNTQVEKLGFIPVNKMKK

918 DNA PAT source 1..918 mol_type unassigned DNA organism unidentified atggaacgggcagcaacaatcggccgccttgacggcaagcagtcaggcggaggtcatgagcgcaggctattctacg acaagtgcgggcggtatctcttcattgcggctgcctttctcatgaccatcatcatcttttccatcatcttcttcgtcggtcgc cagggcctcatgacgttcgcagcggtcagtccgctggagttcttcttcagtgcgagctgggatccgtcgctcggcaagt tcggcgcgctctcgttcatcgtgggctcgctggtgacgacactcctttcggttgccatcggcgcgccgctaggcctgctc ggcgccatcttcctcgcgaaggtcgctccggcctggctcaagaacatcatgcgcccggcgacggatctctacgtcgcc atcccttcggtcgtctacggctacatcggcctgatgctgctcgtgccgtacatgcgcgatgcgttcggcacgacgacgg gcttcggcgtgctcgcggcgtcgctcgtgctcgccatcatgatcatgccgacaatcctctccatcagcacggatgcgctc aatgctgtgccgaagccgctggaggaggcgagcctcgcgctcggcgcgacgtggtggcagacgatggtccacgtca tcgtgcccgctgcagcgcctggcatcctgacggctgtcgtgctcgcgatggcgcgcgccgtcggcgagacgatggcc gtgcagatgctcatcggcaacacgccgcagctcatcacctcgctgttctctccgacggcaacgctgacgagtgacatc gtcgtcgagatgggcaatacgccgttcggctcggtctggggcaatgcgctcttcctcatggctttcgtgctgctcatcct gtcgctggccatgattcttgtcatccgccgtttcggcacgaggagggtataa 305 AA PAT source 1..305 mol_type protein organism unidentified

MERAATIGRLDGKQSGGGHERRLFYDKCGRYLFIAAAFLMTIIIFSIIFFVGRQGLMTFAAVSPL

EFFFSASWDPSLGKFGALSFIVGSLVTTLLSVAIGAPLGLLGAIFLAKVAPAWLKNIMRPATDLY

VAIPSVVYGYIGLMLLVPYMRDAFGTTTGFGVLAASLVLAIMIMPTILSISTDALNAVPKPLEEAS

LALGATWWQTMVHVIVPAAAPGILTAVVLAMARAVGETMAVQMLIGNTPQLITSLFSPTATLT

SDIVVEMGNTPFGSVWGNALFLMAFVLLILSLAMILVIRRFGTRRV 852 DNA PAT source 1..852 mol_type unassigned DNA organism unidentified atgaatgcaaaagtacagaatcaggtggcacgggcgggcctctggtgtacgggattcttcatcctcgccctgcttgcg gctttcctcggctacatcctctacaagggattgccggtgctctcgccgcacttcattctcggcaaatcgagcgacatgat ggctggcggcggcgtcggttcacagcttttcaactcgttctacatgctcttcctctegatggccatttccattccaatcgcg ctcggcgcgggcatctacctcgcggagtacgcgcgtgagaacaagctgacgaagtgcatccgcctttccgtcgagag cctcgcgacggtgccgtccatcgtactcggcctgttcggcatgatcgtcttcgtcaacatgatgaacatgggcttttccat tctcggcggctcgctgacactcgtcctgctgaatctgccgatgctcgtgcgcgtgacggaggaatccatccgcaccgtg ccgaggtcgtatgaagaagcgagccttgcgctcggcgcgacgaagctccagacgatcttcaaggtcgtgctgccgag cgcgatgccgggcatcatcacgggcatcacgctgacggcgggccgtgcactcggcgagacggccatcctgatcttca cggccggcacgacggtatcgcgtcacatgttcgacacggatgtcatggcgggcggcgagacgctggcggttcacctc tggtacctcatgagcacgggcctcgtgccggaccgcgaggccatcgccaacggcatcggcgcactgctgatcctgac gatcctcgtcttcaacttcgtcctgctgctgccgatcaagctgctggggcgcaagacaaaagcatga 283 AA PAT source 1..283 mol_type protein organism unidentified

MNAKVQNQVARAGLWCTGFFILALLAAFLGYILYKGLPVLSPHFILGKSSDMMAGGGVGSQLF

NSFYMLFLSMAISIPIALGAGIYLAEYARENKLTKCIRLSVESLATVPSIVLGLFGMIVFVNMMN

MGFSILGGSLTLVLLNLPMLVRVTEESIRTVPRSYEEASLALGATKLQTIFKVVLPSAMPGIITGI

TLTAGRALGETAILIFTAGTTVSRHMFDTDVMAGGETLAVHLWYLMSTGLVPDREAIANGIGA

LLILTILVFNFVLLLPIKLLGRKTKA 1203 DNA PAT source 1..1203 mol_type unassigned

DNA organism unidentified atgaaagagacaatcaaatccatgcaggcaatcgcggagccgttcttggcattcctgcgctgggaggcgagcagcg gtgtcatcctgctcgcctgcgccatcctcgcactcatcgtggcgaattcaccgctggccgaatcgtacgagcatctgctg cattatcccatcgctgtcggagcgggggagtacgtgctggagatgggcctgctgcactggatcaacgacggcctcatg gcggtgttcttctttgtcatcggccttgagatcaagcgcgagttcctctacggcgagctgcgcacgtattcggcgatgct gctgcccgtcggcgcggcactcggcggcatgctcgtgccggccgccatctatgcggcgatcaacttagggctgccgac attcggcggctggggcatcccgatggcgaccgacatcgcctttgcgctcggcatcatgaccatcgccgcgcgccaggc accgctcggcctcgtcgtcttcctgacagcactcgccatcgtcgatgacctcggcgccatcgtcgtcatcgcgctgttcta caacacggacctcactgtatcggccttgctgctggggctcgtggccgtggctgccgctttcctgctcggccgtttccgcg tgcgcttcctgccggcctacatggcgctcggettecgtcgcctggctggccttcctgaaggcgggcatccacccgacgatt gcgggcgtgctgctcggcctctccatcccggcagcggcggatccggagaactcgctcctgcacaagctcgagcacgc actcgagccgtggtcggcctatgccatcatgccgatcttcgccttggccaacgctggcgtcgcgatctctctggcgacgt ttgacatggcctcgccgatcttcctcggcatcctcgcgggcctctgcctcggcaagcccatcggcatcttcggcgcggta ttcgtgctctgcaaggtctttggcctgcagctgccgggcaatgcgacgaagagccagctcgcggcgacgggcatgctc ggcggcatcggattcacgatgtctatcttcatcgcctcgctggccttcacggacagcgcgatgctcgaccttgcgaaga tcagcatcctctcggcgtcaatcctctcgggcatcctcggtacggctttcttcaagctgcagtcgctcttcggcggggga gaaacggcgcaacagtaa 400 AA PAT source 1..400 mol_type protein organism unidentified

MKETIKSMQAIAEPFLAFLRWEASSGVILLACAILALIVANSPLAESYEHLLHYPIAVGAGEYVLE

MGLLHWINDGLMAVFFFVIGLEIKREFLYGELRTYSAMLLPVGAALGGMLVPAAIYAAINLGLPT

FGGWGIPMATDIAFALGIMTIAARQAPLGLVVFLTALAIVDDLGAIVVIALFYNTDLTVSALLLG

LVAVAAAFLLGRFRVRFLPAYMALGFVAWLAFLKAGIHPTIAGVLLGLSIPAAADPENSLLHKLE

HALEPWSAYAIMPIFALANAGVAISLATFDMASPIFLGILAGLCLGKPIGIFGAVFVLCKVFGLQL

PGNATKSQLAATGMLGGIGFTMSIFIASLAFTDSAMLDLAKISILSASILSGILGTAFFKLQSLF

GGGETAQQ 627 DNA PAT source 1..627 mol_type unassigned DNA organism unidentified atgacaaagatcatttttgtgcgccatggccagaccgagtggaatgtgctcggccgctaccagggccagacggacat cgcactctcgccgctcggcatcgagcaggctgagaagcttgcggcacatttccccgtggacaaggtggaggctgtcta ctcgagcgacctcgtgcgcgccatgatgacggcctgctgcgtcgccgaccgcttcggcctgacagtcgaggcgcgccc cgagttgcgcgagctcaacttcggcgactgggagggcctgacgtacgacgaaatcgtcgccaagtggcccgatgccc tcaataatttcttccagcatcccgacgtcctcgagatcccgcacggtgagagcttcccgaagctgcgcgagcgtgcgct cgatgccgtcgagaagatcgtggcctgccaccctgagcagaccgttgccgtctttgcgcacggcgccattctgcgcac catcctgacggccgccctgcacatggacctcaagtacgtctggaccatccgccagttcaacacggccgtcaacatcgt gacgtacaccgagcacggcacgacagtcgaactgctcaatggcacaggacatctgaagtatgcacaggggactgtg gattaa 208 AA PAT source 1..208 mol_type protein organism unidentified

MTKIIFVRHGQTEWNVLGRYQGQTDIALSPLGIEQAEKLAAHFPVDKVEAVYSSDLVRAMMTA

CCVADRFGLTVEARPELRELNFGDWEGLTYDEIVAKWPDALNNFFQHPDVLEIPHGESFPKLR

ERALDAVEKIVACHPEQTVAVFAHGAILRTILTAALHMDLKYVWTIRQFNTAVNIVTYTEHGTT

VELLNGTGHLKYAQGTVD 750 DNA PAT source 1..750 mol_type unassigned DNA organism unidentified atggcaagaactccaatcattgcaggcaactggaagatgaacaacacgatcgtcgagggcaagaacctcgtccgcg gcctggctccgctcgtcaaggatgccaaggtgacggtcgtcgtctgcccgacggctacggctctcgcagctgtcgcag atgcagcactcggcacgaacatccacgtcggcgcacagaacgttcattgggaagatcacggcgcgttcacgggcga gatctccacgggcatgctcaatgagatcggcgtagattactgcgtcctcggccacagcgagcgccgcggttacttcgg cgagacggatgagggcgtcaacaagcgcgctcatgctgctttcgctgcaggcatcacgccgatcatctgctgcggtga gtccctcgagcagcgcgaagctggtgtatacctcgacttcgtcgctggtcaggtcaaggctgccctcgctggcttccag ccggaagaagtagcaaagatcgtcatcgcttacgagccgatctgggctatcggcacgggcaagacggcttccttcga gcaggctgaggaagtctgcgcgcacatccgcaagacggttgccgcagaattcggccaggaagcagctgacggcatc cgcatccagtacggcggcagcgtcaagccggctacgatcaaagacctcatgaagcagccgaatgtcgatggcgccct cgtcggcggtgcatcgctcaaggctaaggacttcagcgagatcgtaaacttctga 249 AA PAT source

1..249 mol_type protein organism unidentified

MARTPIIAGNWKMNNTIVEGKNLVRGLAPLVKDAKVTVVVCPTATALAAVADAALGTNIHVGA

QNVHWEDHGAFTGEISTGMLNEIGVDYCVLGHSERRGYFGETDEGVNKRAHAAFAAGITPII

CCGESLEQREAGVYLDFVAGQVKAALAGFQPEEVAKIVIAYEPIWAIGTGKTASFEQAEEVCA

HIRKTVAAEFGQEAADGIRIQYGGSVKPATIKDLMKQPNVDGALVGGASLKAKDFSEIVNF

1302 DNA PAT source 1..1302 mol_type unassigned DNA organism unidentified atgaaagcatacttacagatcatgcaggtcatcggccgtgaaatcatcgattcgcgcggcaatccgacggtcgaggc ggaagtcacgctcgaggacggctccgtcggccgcgcatctgctccgtecgggcgcttcgacgggcgagttcgaggcgc tcgagctccgcgacggcgacaaggcgaagttcggcggcaagggcgtctcgaaagctgtcgcgaacatcaatgaga agatcgccccggctctcatcggtgcggatgcgtcggacatctatgcagtcgatgccatcatgctcaaactcgacggca cggaagacaagtcgaacctcggcgcgaacgccatcctcgccgtctcgctcgcagcggcaaaggccgcggccgtatc gctcgacctcccgctctaccgcttcctcggcggcatcagcggcaatcacctgccggtgccgatgatgaacatcttgaac ggcggcgcgcatgcgacgaactcggtcgacacgcaggagttcatgatcatgccggccggcgcaccgtccttccgcga gggactgcgctgggcgacggaggtcttccatgcgctgcaggcgctgctcaagaaggaagggcagacgacggctgtc ggcgatgagggcggctttgctccgaacctcaagagcgacgaggacacgatcgagcacatcctgacggccatccgca atgcgggttacgagccgggccgcgacttcgtgctggcgatggatgcggcttcgtcggagtggaagagcgagaaggg caagggcttctacaagcagccgaagtcgggcaaggagttcacgtcggatgagctcatcgcgcactggaagagcctc atcgagaagtacccgatctactccattgaggacggcctcgatgaggaggactgggaaggctggcagaagatgacga aggagctcggcgacaaggtacagctcgtcggcgatgacctctttgtcacgaacacgaagcgcctgaagaagggcat cgagctcggctgcggcaacagcatcctcatcaagctcaaccagatcggcacgctgtcggagacgctggaggccatca agatggcacatgaggcgggctacacggccatcgtctcgcaccgttcgggcgagacggaggacacgacgatcgcgg acctcgctgtcgcgctcaacacgaaccagatcaagacgggcgccccgtcccgctcggagcgcgtcgccaagtacaac cagctgctgcgcatcgaggaagagctcggcgcaagcgcggtctatccgggcaaagcagcttttagattccagaagta a 433 AA PAT source 1..433 mol_type protein organism unidentified

MKAYLQIMQVIGREIIDSRGNPTVEAEVTLEDGSVGRASAPSGASTGEFEALELRDGDKAKFG

GKGVSKAVANINEKIAPALIGADASDIYAVDAIMLKLDGTEDKSNLGANAILAVSLAAAKAAAV

SLDLPLYRFLGGISGNHLPVPMMNILNGGAHATNSVDTQEFMIMPAGAPSFREGLRWATEVFH

ALQALLKKEGQTTAVGDEGGFAPNLKSDEDTIEHILTAIRNAGYEPGRDFVLAMDAASSEWKS

EKGKGFYKQPKSGKEFTSDELIAHWKSLIEKYPIYSIEDGLDEEDWEGWQKMTKELGDKVQL

VGDDLFVTNTKRLKKGIELGCGNSILIKLNQIGTLSETLEAIKMAHEAGYTAIVSHRSGETEDT

TIADLAVALNTNQIKTGAPSRSERVAKYNQLLRIEEELGASAVYPGKAAFRFQK 1194 DNA

PAT source 1..1194 mol_type unassigned DNA organism unidentified atgaacaagaaaaccatcaaagacgttgacgtaaacggcaagaaagtattcgtccgcgtcgactacaatgtcccgtt cgacgacaagatgaacatcacgaacgacacgcgcatggtccgcacgctgccgaccctgaactacctgctcgaccacg gtgcagctctcgtcatcgcctgccacatcggccgtccgaccgaggcgcgcgaggacaagttctccacaaagtacctcg tcaagcacctctccgagctgctcggccgcgatgtcaagtgggcctccgactgcgtcggcgctgaggcagatgccgca aaggctgcgctgaagccgggcgaagtcctgctgcttgagaacctccgttaccacaaggaagagaagaagaacgatc ccgagttcgcgaagcagctcgcttceggttgcgatctcgcagtcgacgatgctttcggtgtttcccaccgcgctcatgctt cgaacgcaggcgttccgaagtacatcgagacggttgctggcttcctgatggaaaaggaaatcaactacatcggcaag acgctcgagaacccgcagcatccgttcgtcgccattatcggcggtgcaaaggtctccgataagatcggcgtcatcagc aacatgatcgacaaggttgacacgatcatcatcggcggcggcatggctcatacgtttgatgcagccaagggcctgcc gattggcgattccctctgcgagccggacaagtacgatctcgctcgtgagctgctcaagaaagcagaagacaagggcg tcaaggtcgtcctgccggtcgacctcgtcattgccgacaagttcgctgccgatgccaacacgaagacggttgacgtcg acaaagtaccggatggctggcaggcactcgattccggcgagaagacgtcggaagagtacacgaaggctcttgaag gcgctaagacggtcatctggaacggaccgatgggcgtattcgagtttgatgcttttgcaaaaggcacgctcgctgttgc taaggctgtcgccaaggctacggaaaatggcgctatctccatcgtcggcggcggcgactccgttgcagccctcaaga agacgggcctgacggacaagatctcgcacgtctccacgggcggcggcgctacgctcgagttcctcgaaggcaaaga gatgccgggcatcgcagcactggctgacaaataa 397 AA PAT source 1..397 mol_type protein organism unidentified

MNKKTIKDVDVNGKKVFVRVDYNVPFDDKMNITNDTRMVRTLPTLNYLLDHGAALVIACHIG

RPTEAREDKFSTKYLVKHLSELLGRDVKWASDCVGAEADAAKAALKPGEVLLLENLRYHKEEK

KNDPEFAKQLASGCDLAVDDAFGVSHRAHASNAGVPKYIETVAGFLMEKEINYIGKTLENPQH

PFVAIIGGAKVSDKIGVISNMIDKVDTIIIGGGMAHTFDAAKGLPIGDSLCEPDKYDLARELLK

KAEDKGVKVVLPVDLVIADKFAADANTKTVDVDKVPDGWQALDSGEKTSEEYTKALEGAKTV

IWNGPMGVFEFDAFAKGTLAVAKAVAKATENGAISIVGGGDSVAALKKTGLTDKISHVSTGG

GATLEFLEGKEMPGIAALADK 1428 DNA PAT source 1..1428 mol_type unassigned

DNA organism unidentified atgttaaagaagacgaaaattatctgcacgcagggtcctgctacggagagaccgggcgtagtcgatgcactgattgc aaacggcatgaactgtgcacgctttaacttctcccatggtgaccacgcagagcacctcaaccgcatcaacatggtgcg cgaggctgccaagaaggccggcaaggtcatttccctgattctcgatacgaagggaccggagatgcgcctcggcgagt tcaaggacggcaaggtcatgctcgagaagggcaatcagttcacgctgacgtatgaggacatcccgggcgatgagac gcatgtctccgtcaaccacaagggcctctacacggaagtcaagccgggtgacacgctgctcctctctgatggcctcgta gcactcaaggtcgatgagatccgcggcaaggacatcatcacgacgatccagaacagcggcaagatgagcacgaag aagcgcgtcgctgctccgggcgtatccctcggcctgccgccgatctcggagcaggatgcgaaggacatcatcttcggc tgcgagcaggacctcgatttcgtcgctgcttcctttatccagcgtccggaggacgtcctggccatccgcaagctcatcga ggagcacaatggccacatggagatcatgccgaagatcgagaacctcgaaggcgtcaagaacttcgatgcgattctc gaagtctccgacggcatcatggtcgctcgcggtgacctcggcgttgaggttccggccgaggacgttccgctgatccag aaagagatcatccgcaagtgcaacaaggctggcaagccggtcatcgtcgctacgcagatgctcgactccatggagcg caacccgcgcccgacgcgcgctgaggtctccgatgtcggcaacgccatcctcgatggtacggatgccatcatgctctc cggcgagacggcttccggcgattacccggtcgaggctgtttccacgatgaaccgcatcgcttgccgcatcgaggagtc cctcgagtacaagaatctcttcgttgagcgcggcttcgagcacagccagagccgcacgcgcgccgtcgcacatgctac ggtacagatggcttacgagctcgatgtcccggctatcatcacgccgaccgacagcggctacacgacgaagatcgtatc ccgttaccgtccgaaagcagctatcgttgcctacacgccgcatgagaaggtcgtccgccagctcaacctccgttgggg cgtatacccgatcctcggcacgcagtggaaggacgtcgacgagatgattgcgaacgctgtttccgcagctgtcaagg acggcttcgtgaagcgcggcgacacgacgatcatcacgtccggcatcaagctccagagcaagacgagcgtcggcaa caacacgaacatgatccgcgtctacaagatctga 475 AA PAT source 1..475 mol_type protein organism unidentified

MLKKTKIICTQGPATERPGVVDALIANGMNCARFNFSHGDHAEHLNRINMVREAAKKAGKVIS

LILDTKGPEMRLGEFKDGKVMLEKGNQFTLTYEDIPGDETHVSVNHKGLYTEVKPGDTLLLSD

GLVALKVDEIRGKDIITTIQNSGKMSTKKRVAAPGVSLGLPPISEQDAKDIIFGCEQDLDFVAA

SFIQRPEDVLAIRKLIEEHNGHMEIMPKIENLEGVKNFDAILEVSDGIMVARGDLGVEVPAEDV

PLIQKEIIRKCNKAGKPVIVATQMLDSMERNPRPTRAEVSDVGNAILDGTDAIMLSGETASGD

YPVEAVSTMNRIACRIEESLEYKNLFVERGFEHSQSRTRAVAHATVQMAYELDVPAIITPTDSG

YTTKIVSRYRPKAAIVAYTPHEKVVRQLNLRWGVYPILGTQWKDVDEMIANAVSAAVKDGFVK

RGDTTIITSGIKLQSKTSVGNNTNMIRVYKI 1017 DNA PAT source 1..1017 mol_type unassigned DNA organism unidentified atggcagtaaaagttgctatcaatggttttggccgtatcggtcgtctcgcattccgtcagatgttcgatgctgagggttat gaagtcgttgcaatcaacgatctcacgagcccgaaaatgctcgcttacctgctgaagtacgattcttcccagggcaagt acgagtatgctgacacggttgaggctggcgaagacagcatcacggtcaagggcaagacgattaaaatctatgccga gaaagatgcaaagaacatcccctgggcgaagcatgatgtagatgtcgttctcgagtgcacgggcttctacacgtccaa ggaaaaggcttccgcacatctcgaagctggcgctaagaaagtcgtcatctccgctccggcaggcaaggacctcccga cgatcgtgttcaacacgaaccacaagtccatcccggcaggcacgaaaatcatctccgctgcatcctgcacgacgaact gcctcgcaccgatggcaaaggccctcaatgaccttgctccgattcagagcggcatcatgcagacgatccacgctttcac gggcgaccagatgacgctcgatggcccgcagcgcaagggtaacctccgccgcagccgtgctgcttccgagaacatc gttccgacgtcctccggcgcagctaaagctatcggcctcgttcttccggaactcgatggcaagctcatcggtgctgcac agcgcgttccgaccccgacgggttccacgacgctcctctacgctgttgtcaagggcaacgttacggttgacgaagtca atgcacagatgaagaaggagtccacggagtccttcggctacaacacggatgacattgtatccaaggatgttgtcggt atgcgttatggctccctgttcgatgctacgcagacgatggtcagcccgatggctgatggcaacacgctcgttcaggttg tatcctggtacgacaacgagaactcctacacgagccagatggttcgcacgatcaagtacttcgctgaggaagtcaagt aa 338 AA PAT source 1..338 mol_type protein organism unidentified

MAVKVAINGFGRIGRLAFRQMFDAEGYEVVAINDLTSPKMLAYLLKYDSSQGKYEYADTVEAG

EDSITVKGKTIKIYAEKDAKNIPWAKHDVDVVLECTGFYTSKEKASAHLEAGAKKVVISAPAG

KDLPTIVFNTNHKSIPAGTKIISAASCTTNCLAPMAKALNDLAPIQSGIMQTIHAFTGDQMTLD

GPQRKGNLRRSRAASENIVPTSSGAAKAIGLVLPELDGKLIGAAQRVPTPTGSTTLLYAVVKGN

VTVDEVNAQMKKESTESFGYNTDDIVSKDVVGMRYGSLFDATQTMVSPMADGNTLVQVVS

WYDNENSYTSQMVRTIKYFAEEVK 1299 DNA PAT source 1..1299 mol_type unassigned DNA organism unidentified atgaaaaaattccaagtcgtcgtgaagtgctcactcggtatccatgcgcgtcccgcagctcagatcgcgcaggcatgc agcaacctgcgggcggcggtgacgctcgaggtcgataatgagactgcccagggcaacaacgtgctggagatcttga acctccacgctccgaaaggcgcaacggtcaatgtcaccgtggacggccctgatgaggaagaggctgcacagcagat ccaggctgttttcgatgccatgggcccgaaggagaagaagggctctgtcctcaaggtcgcctttttcggcacgaaaga ctatgaccgcctctatttcagcgagctcgcaaaggacaagggcgagggcacgtacaacgtcgaactcaagtatttctc gagccgcctgacggatgagacggcacatctcgccaacggctatgacgctgtctgcatcttcgtcaacgacgaggcac cgcgttctgtcatcgagcagctgcatgacggcggcgtccgcctgatcctcctgcgctgcgccggcttcaacaatgtcga caagaaggccgctgccgagtacggcatcacggtcctgcgcgtaccggcttactccccgtacgcagtggcagagcatg ccatggcgacgctgcaggctgcaaaccgccgcctgcacaaggcatacaacaaggtgcgcgacaacaacttcgacct cacgggcctgctcggcgtcgatctccacaacaaggtcgccggcatcctcggcacgggccgcatcggccagtgcatgg cgcgcatctgcaagggctacggcatgacggtcatcggctgggatgcgttcccgaacaagaagctcgaggaagaggg gctgctcacctatgcttcgaaggaagaggtcctgaagcgctctgacctcatctccattcacgcaccgctcatcatgggc gaaggcggcacgtatcatctcattgatgagaaggccatctccctcatgaaggacgatgtcatgctcacgaatgctgca cgcggcggcctcatcgatacggaagcgctcattgccgcgctcaagaagggcaagttccatgcggttgcgctcgacgtc tacgagggcgaggatgccaatgtctacacggaccacagcttcgacgtcccgacggaggatgtcacgggccgtctgct catgttcccgcaggtcatcctcacgagccatcaggcattctttacgcgcgaggcactgcaggccatcgcgacggtgac gatggagaacgcccgcaatttcaacgagggccgtccgttcggtgctgctgaggtgaaataa 432 AA PAT source 1..432 mol_type protein organism unidentified

MKKFQVVVKCSLGIHARPAAQIAQACSNLRAAVTLEVDNETAQGNNVLEILNLHAPKGATVNV

TVDGPDEEEAAQQIQAVFDAMGPKEKKGSVLKVAFFGTKDYDRLYFSELAKDKGEGTYNVEL

KYFSSRLTDETAHLANGYDAVCIFVNDEAPRSVIEQLHDGGVRLILLRCAGFNNVDKKAAAEY

GITVLRVPAYSPYAVAEHAMATLQAANRRLHKAYNKVRDNNFDLTGLLGVDLHNKVAGILGTG

RIGQCMARICKGYGMTVIGWDAFPNKKLEEEGLLTYASKEEVLKRSDLISIHAPLIMGEGGTY

HLIDEKAISLMKDDVMLTNAARGGLIDTEALIAALKKGKFHAVALDVYEGEDANVYTDHSFDV

PTEDVTGRLLMFPQVILTSHQAFFTREALQAIATVTMENARNFNEGRPFGAAEVK 3525 DNA

PAT source 1..3525 mol_type unassighed DNA organism unidentified atgagcaaaaagatgaaaaccatggacggcaacacagctgccgcctacatctcctatgctttcaccgacgtcgcggc gatctacccgattacgccgtcctcgccgatggctgagcatgtagatgaaatggctgccaagggagcgaagaatctctt cggccagaaggtcaaggtcatcgagctgcagtctgaggccggcgctgccggcgctgtgcacggctcgctgcaggcc ggtgcactgacgacgacgtacacggcttcccagggcttcttgctgatgatcccgaatctctacaaggtagccggcgag ctgttgccgggcgtcttccacgtctccgcgcgcgcactcgctgccaactccctgaacatcttcggcgaccaccaggatgt catggccgcacgccagacgggttgcgccatgctcgccgaggcgagcgtccaggaggtcatggacctctcggccgtcg cacacctcgtcgccatcaagggccgcgtgccgttcatcaacttcttcgacggcttccgcacgtcgcacgagatccagaa gatcgagacgattgactacgaagacctcgcaaagctgctcgactgggatgccgtcaaggccttccgccgccgcgctct gaacccggaccacccggtcctgcgcggctccgcgacgaacccggacatctacttccagtcgcgtgaagcagccaaca gcttctacgatgcgctgccagagctcgtcgaggaggccatggctgacctcgcgaaggtcacgggccgcgagcaccat ctctttgactactatggcgccaaggatgccgaccgcatcatcatcgcgatgggctccgtctgccagacggtccaggag acggtcgactacctcaacgcgaagggggagaaggtcggcctgctgaacgtacacctctaccgtccgttctccatcgag cacttcttcaagttcctgccgaagaccatcgagaaagtcgccgtcctcgaccacacgaaggagccgggttcgctcggc gagccgctctacctcgatgtcaaggcagccttctatcattccgacatgcacccgacgatcatcggcggccgcttcggcc tcggcggcaaggacacgacgccggaccagatcttcgccgtctttgaagagctcaagaaagacgcgccgaaggacg gtttcacgatcggcatcgacgacgatgtcacgcacacgagcctgacgccggcgctgacggatgtcgacctcacgccg gaaggcacgacggcctgcaagttctggggcctcggctcggatggcacggtcggcgccaacaagagcgccatcaag atcatcggcgacaagacggacatgtacgcccaggcgtacttcgcctatgactccaagaagtcgggcggcatcacgat gtcgcacctgcgcttcggcaagtccccgatcacgagcccgtacctcatcaacaaggccgacttcatctcctgctcgcag cagtcgtacgtctacaagtacgacctgctcgccggcctcaagaagggcggcacgttcctcctcaacacggtctggagc gacgagaagctcacgaagcacctgccggcagccatgaagcgctacatcgccaagaacgagatccagttctacacgg tcaacgctgtctccatcgccaagggcctcggcctcggcggccgcttcaacatggtcatgcagtccgcgttcttcaagctc gcgaacatcatcccgatcgagacggccgtgacctacctcaaggaagccgtcgtcacctcgtacggccgcaaaggcca gaacatcgtcgacatgaacaacggcgccatcgaccagggcatcgaggccctgcacaaggtcgaggtgccggcatcg tgggctgatgctgaagacgagccgcaggagaagcgcgacctgccggagttcatcaccgaggtccaggaagtcatga accgccaggaaggcgacaagctgccggtctcgaagttcgccggcgaccgcgccgacggcacgtacccgctcggcgg cgccgcctacgagaagcgcggcacggccatcaacgtgccggtctggaacgcccagaagtgcatcggctgcaacaag tgctcctatgtctgcccgcacgcttcgatccgtccggtcctcacgaccgacgaagagctcgctgcagcaccggagggct tcccgtccaaggaagtccgcgccgtcaaggactaccacttcacggtggctgtctccacgatggactgcctcggctgcg gcaactgcgcgcaggtctgcccggtcaaggcgctcgacatgacgccgcttgacgacgacctcaaggcaaagcaggc ttacttcgactacggcgtcgacacggagaaagtcgcgccgaagaagaacccgatgaagaaagagaccgtcatcggc agccagttcgagcagccgctcatcgagttctccggcgcctgcgccggctgcggcgagacgccgtacgccaagctcatc acgcagctcttcggcgaccgcatgatgattgccaacgccacgggctgcacctccatctggggcggcagcgcaccggc catgccgtacacgacgaacgccaagggccacggcccggcttgggacaactccctgttcgaggacaacgcagagttc ggcctcggcatgttcctcggcacgcagtccgtccgcaatggcctcgccgatgacgccaagaaggccatcgaagaagg tcttggcagcgaagacctccaggcagccctcaaggactgggtagagaacctcgacaacggcaacggcacgcgcgac cgcgccgaccgcctcgaagccctgctcgcagccgagaagggtgacaatgcgctgctcaacaagctctacgagaacc gcgactacttcgtcaagcgctcccagtggatcttcggcggcgacggctgggcctacgacatcggctacggcggcgtcg accacgtcctcgcctccggcgcagacgtcaacgtcttcgtcttcgacaccgaagtctactccaacaccggcggccagg cctccaaggccacgccggcagcagcaatcgcacagttcgccgcaaccggtaagaagacccgcaagaaggatctcgg cctcatggccaagacctacggctacgtctacgtcgcccaggtcgccatgggcgcagaccagaaccagctgctcaagg ccatcaccgaggccgaggcttatccgggcccgtccctcatcatcgcctacgcaccgtgcatcaaccacggcatccgca agggcatgggctgcagccagctcgaggagaaactcgccgtagagtgcggctactgggcaaactaccgctacaaccc gcagctcgtcggcaccgacaagaacccgttcagcctcgactccaaagagccggacttctccaagttccaggacttcct catgggcgagaaccgctacatcaacctcaagcgcaccttcccagaagcagccgaagccctctttgagaagacccagc gcgacgccgagatccgctacaacaactacaagaccctcgccggcaaataa 1174 AA PAT source 1..1174 mol_type protein organism unidentified

MSKKMKTMDGNTAAAYISYAFTDVAAIYPITPSSPMAEHVDEMAAKGAKNLFGQKVKVIELQS

EAGAAGAVHGSLQAGALTTTYTASQGFLLMIPNLYKVAGELLPGVFHVSARALAANSLNIFGD

HQDVMAARQTGCAMLAEASVQEVMDLSAVAHLVAIKGRVPFINFFDGFRTSHEIQKIETIDYE

DLAKLLDWDAVKAFRRRALNPDHPVLRGSATNPDIYFQSREAANSFYDALPELVEEAMADLAK

VTGREHHLFDYYGAKDADRITIAMGSVCQTVQETVDYLNAKGEKVGLLNVHLYRPFSIEHFFKF

LPKTIEKVAVLDHTKEPGSLGEPLYLDVKAAFYHSDMHPTIIGGRFGLGGKDTTPDQIFAVFEE

LKKDAPKDGFTIGIDDDVTHTSLTPALTDVDLTPEGTTACKFWGLGSDGTVGANKSAIKIIGD

KTDMYAQAYFAYDSKKSGGITMSHLRFGKSPITSPYLINKADFISCSQQSYVYKYDLLAGLKK

GGTFLLNTVWSDEKLTKHLPAAMKRYIAKNEIQFYTVNAVSIAKGLGLGGRFNMVMQSAFFKL

ANIIPIETAVTYLKEAVVTSYGRKGQNIVDMNNGAIDQGIEALHKVEVPASWADAEDEPQEKR

DLPEFITEVQEVMNRQEGDKLPVSKFAGDRADGTYPLGGAAYEKRGTAINVPVWNAQKCIGC

NKCSYVCPHASIRPVLTTDEELAAAPEGFPSKEVRAVKDYHFTVAVSTMDCLGCGNCAQVCPV

KALDMTPLDDDLKAKQAYFDYGVDTEKVAPKKNPMKKETVIGSQFEQPLIEFSGACAGCGETP

YAKLITQLFGDRMMIANATGCTSIWGGSAPAMPYTTNAKGHGPAWDNSLFEDNAEFGLGMFL

GTQSVRNGLADDAKKAIEEGLGSEDLQAALKDWVENLDNGNGTRDRADRLEALLAAEKGDN

ALLNKLYENRDYFVKRSQWIFGGDGWAYDIGYGGVDHVLASGADVNVFVFDTEVYSNTGGQ

ASKATPAAAIAQFAATGKKTRKKDLGLMAKTYGYVYVAQVAMGADQNQLLKAITEAEAYPGPS

LITAYAPCINHGIRKGMGCSQLEEKLAVECGYWANYRYNPQLVGTDKNPFSLDSKEPDFSKFQ

DFLMGENRYINLKRTFPEAAEALFEKTQRDAEIRYNNYKTLAGK 1530 DNA PAT source 1..1530 mol_type unassigned DNA organism unidentified atggtagatatcctcgatcgtgtgcgcaacaaggcgctgcagtccaagatcgtgacaccggaggaagcggcagactt catcaagccgggcatgacccttgcgacgagcggcttcacatcctcggcctacccgaaggcggtgccgctcgctctcgc ggaccgcatgaagaaggacccgttcacggtcaacatcatgacgggcgcttcgacgggcccggagttcgatgaagcg ctcgcctcggtccacggcatcaagaaacgcctgccgttccagacggacaaggtgctgcgcagccagatcaacgacgg cacggtcgattacatcgacatacatctgtcggaggtcgcgcagctctcgcgctgcggctacctcggccatctcgacgtc gccgtcatcgaggcctgcgccatcacggaggagggcaacatcatcccgacgacggccgtcggcaactcggcctcgtt cgtgcagacggccgacaccgtcatcatcgaggtcaacaacgcgcagccgctggagttcgagggcatgcacgatgtct acctgccgctcgacccgccgaaccgtctgcccatcccgatcgtgcgcgtcgacgaccgcatcggcacgccgtacatcc cgtgcccgcaggacaagatccgctacatcgtgccgtgcgacatcgcggaccacacgcgctcgctcgcgccgctcgac gcgacggcgcagcagatggctgacctgacgattgacttcctcaagcgcgagataaaggctggccgcatgccgaaga acctgctgccgatacagtcgggcgtcggcaatgtcgccaatgccgtcacggcgggctttgtccgctcggacttccgcg acctcacggtctacacggaggtcatccaggacggcatgctcgacctcatcgatgcgggcaagctcaacttcgcctcgg gcacggccttctcgccgtctcctgagggcatggcgcgcttcttcaaggacattgagaagtacaagaagtacatgatcct gcgcccgcaggagatctcgaacagcgcggaggtcatccgccgcctcggcgtcattgcgatgaacacggccgtcgaa gtcgacatctacggcaacgtcaactcgacgcacatcgcgggcacgcacatgatcaacggcatcggcggcagcggcg acttcgcgcgcaacgcctacctgaccatcttctacacgccgtcggtggccaagggcggcaagatctcggccgtcgtgc cattctgctcgcatgttgaccagccggagcacgacgtcgacgtcatcatcacggagcagggcgtggccgacctgcgc ggcaagtcgccgcgccagcgcgccaaggagatcatcgagaactgcgcgcaccccgacttccgcccaatgctgcgcg actatttccagcgcgccgacgcgaagacgaaccacgcgcacacgccgcacctcctcgatgaggccttctcgttccacc agcgctatctggagacaggcagcatgaagcgcgagagtcaggaagatacaggaaaggtgtga 509 AA PAT source 1..509 mol_type protein organism unidentified

MVDILDRVRNKALQSKIVTPEEAADFIKPGMTLATSGFTSSAYPKAVPLALADRMKKDPFTVNI

MTGASTGPEFDEALASVHGIKKRLPFQTDKVLRSQINDGTVDYIDIHLSEVAQLSRCGYLGHL

DVAVIEACAITEEGNIIPTTAVGNSASFVQTADTVIIEVNNAQPLEFEGMHDVYLPLDPPNRLPI

PIVRVDDRIGTPYIPCPQDKIRYIVPCDIADHTRSLAPLDATAQQMADLTIDFLKREIKAGRMPK

NLLPIQSGVGNVANAVTAGFVRSDFRDLTVYTEVIQDGMLDLIDAGKLNFASGTAFSPSPEGM

ARFFKDIEKYKKYMILRPQEISNSAEVIRRLGVIAMNTAVEVDIYGNVNSTHIAGTHMINGIGG

SGDFARNAYLTIFYTPSVAKGGKISAVVPFCSHVDQPEHDVDVIITEQGVADLRGKSPRQRAK

EIIENCAHPDFRPMLRDYFQRADAKTNHAHTPHLLDEAFSFHQRYLETGSMKRESQEDTGKV

1026 DNA PAT source 1..1026 mol_type unassigned DNA organism unidentified atgattaaagttggtattatcggtgcaggccgtatcggtcatgtacatggcgagagcatctcgaagttcgtcaagaacg caacggtcaagacgattgctgatccgttcatgaacgagaagacggaagcttgggcaaagtccctcggcatcgagaa gacgacgaaagattaccatgagatcctcaacgatcctgaaattgaagccgtcctgatctgcgcttccacggaccagca ttccccgctctccatcgaagcactgcgcgccggcaagcacgtcttctgtgagaaaccgattgaccatgatgtcaataag atcaaggaagttctcgacgtcgtcaaagagacgggcaagaaataccaggtcggcttcaaccgccgctttgaccacaa cttcaaggctatccgcgatgctgtcgtcgccggaaaagtcggcaagcagcagatcatcaagatcacgtcccgtgatcc ggaaccgccttccatcgattacgtaaagatttccggcggtatcttcctcgacatgacgattcatgatttcgatatggtccg ctatctctccggcgcagaagtcgaggaagtatatgcagagggctctgtcaccgtcgatccggaaatcggcaaggctg gcgacatcgatacggccatcatcacgctgaagctcgacaatggcgctacggctgtcatcgacaactgccgtgccgctt gctatggctatgaccagcgcgctgaagtcttcggcacaaagggctgcgtcgccatctccaacgattcggattccaatgc agtctacagctgcaaggacggcgtcatcgccgagaagccgatgttcttctttctcgagcgctacatgatggcttatgca aacgaagtcaatcagttcgtcgaagcgatcgtcaacgacacgccgaccccggtcaatgcaaacgacggcctgcagc cggtcctcattggcctcgctgccaagaagtcggtcgaagagcatcgcccggtcaagattgcagagatccgcgcccagt acggcctctga 341 AA PAT source 1..341 mol_type protein organism unidentified

MIKVGIIGAGRIGHVHGESISKFVKNATVKTIADPFMNEKTEAWAKSLGIEKTTKDYHEILNDP

EIEAVLICASTDQHSPLSIEALRAGKHVFCEKPIDHDVNKIKEVLDVVKETGKKYQVGFNRRFD

HNFKAIRDAVVAGKVGKQQIIKITSRDPEPPSIDYVKISGGIFLDMTIHDFDMVRYLSGAEVEE

VYAEGSVTVDPEIGKAGDIDTAIITLKLDNGATAVIDNCRAACYGYDQRAEVFGTKGCVAISN

DSDSNAVYSCKDGVIAEKPMFFFLERYMMAYANEVNQFVEAIVNDTPTPVNANDGLQPVLIGL

AAKKSVEEHRPVKIAEIRAQYGL 3426 DNA PAT source 1..3426 mol_type unassigned

DNA organism unidentified atgaagaacattcgcaagatcttggtgccgaaccgcggcgagattgccatccgcattttccgcgcctgccacgagatg ggcatccgcacggtcgcggtctactcgaaagaagatgtcctgtcgctgcatcgcagccgcgccgatgaagcgtatctc gtcggcaagggcaagaagccagtcgatgcctacctcgacatcgaggacatcatccgtatctgcaaagagcacgatgt cgatgccatccatccgggctacggcttcctctccgagaacgcacagctggccaagcgctgcgaggatgagggcatca tcttcatcggcccgaaagttgagcacctgcagatgttcggcgacaaggtcaacgcgcgcatccaggcagagcgcgcc gacatcccgatgatcccgggcacgaacggtgccgtcaaggatttcgctgaggtcaaggccttcgctgagcgcgtcgg cctgccgatcatgatcaaggccatcaacggcggcggcgggcgcggcatgcgccgcgtcgaccgcatggaagacctc aaagaggcgtacgatgaggcgcgctcggaggccaagcgtgccttcggcgatgaggatgtctacgtcgagaagtgca tcctaaacccgaagcacatcgaagtgcagatcatgggcgatgaacacggcaatgtcatccacctcaatgagcgcgac tgctccatccagcgccgccaccagaaagtcatcgagatggcaccggcatggtcgctgccgaagaagctgcgccaga atatctgcgctgctgcgctgaagatcatgaagaatgtccactacgtcaacgccggcacagtcgaattcctcgccgacc aggatgaggagcacttctacttcatcgaagtcaacccgcgcgtccaggtcgagcacacggtcaccgaggccatcacg gacatcgacatcgtcaagacgcagatcctcgtcgccgagggccatgcgctctccgacccagagatcggcatcaagag ccaagaagacatcccctgcaacggcgtggccatccagtgccgcatcacgacggaggacccgcagaacaacttcatg ccggacaccggcaagatcaacgactaccgcagcggcggcggccctggcatccgcctcgatgccggcacggcctaca cgggcgccgtcatcacgccgtactacgactccctgctcgtcaaggtcacggcgcatgccaacaacgccccggagaca atctaccgcatgctgcgctgcctcgatgaattccgcatcggcggcgtcaagacgaacatctacttcctcaagaacatgc tgctcgacaagaacttccaggctggcagctgcaacgtcaactacatcgaccaccatccggacctgctcaacgccccgc aggtcatcgatgagccggcagccggcctgctcgcctacatcggtgaggtcacggtcaacggcttccacggcaacggc tcaaacccgaagccgcgcttcgagacgccggtgaagctcaatgccgccgacgaagcctgcccgtccggcacgcgcc agctcctagaggagctcggccccgagaagttctccaagtggatccaggaccagaagcaggtcctgctgatggacac gacgtaccgcgatgcccatcagtccctgctcgccacgcgcatccgcacgcgcgacatcatgcaggccatccactacac ggcctgcaaggtcccgcagatctacgcctttgaggactggggcggcgcgacgttcgatgtcgcctaccgtttcctcgac gaggacccgtgggagcgcctgcgcaagatgcgcgaggctgcgccgaacatcctgttccagatgttgacgcgcggcg ccaacaccgtcggctacacgaactatccgcctgaagtcgtgcgccagttcctcgccctecgcggccaagaacggcgtcg atgtcttccgcatcttcgactgcctgaaccagctcgaccacatgacgctgtcgattgacgaagtccgcaagcagggca agctcgcggagacggccttctgctacacgggcgatatccttgacgacggccgccagaagtacacgctgaagtactac acgaatctcgccaaggagatggaaaaggccggtgccaacatcatcgccatcaaggatatggccggcctcctgaagc cagaagcggcctacaccctgatctcggccctcaaggatgctgtcgacctgccgattcacctgcacagccacgagggtg gcggctgcacgctctacacctacgccaaggcggcagaggccggcgtcgacatcgtcgatgtcgccacgagcgccctc tccaacggcacgagccagccgtccatgacggccttcatccaggcgctctccaacaacccgcgccagccgcagatgga catcgaggaactcgagacgattgaccgctactggcaggtcgtccgcgcctactacgcgggtgtcgacggcaagatga cgagcccgaacacgacggtcttccagcacgagatgcctggcggccagtacacgaacctgcgccagcaggcgaagg gcgtcggcctcggcgacagatggccggaagtctgccgcatgtacgccaaggtcaacgagatgttcggcgatgtcatc aaggtcacgccgtcctcgaaagtcgtcggcgacatgacgctcttcatggtccagaacaacctgaccgagaaagatat ctacgagcgcggcgagacgatggacttcccgaaatccgtcgtcgacttcttcgacggcaagctcggcgtcccctacgg cggcttccccgagaagctccagaagatcatcctcaggggcgagcagccgcacctcgagacgccgccegccccgatc gaccaggagaaggtcacgcaggacatgaaggccctgcgcatgccggagacggaagaggcgcgctcgagctactg catctacccgaaggtctacaaggactacatccagcgctaccatcagtacggcgacctttccatcctcgacacgccgacg tacttcttcggcatgaagccgggcgaggagagctggctgcgcatcggcggcaagatggtcctcatccgcatgaacta catcacgccgccgtcggatgatggcttccgcgagatccagttcgaggtcaacggcatgccgcgcgagatccgcgtgc gcgataaggcggcttcggaaggcgcggcgatcatccgccaggccgacccgactgtcccgggcgaagtagccgctac gctctctggctctgtcctgcgcctcatcgcagccaagggcgatgtcgtcaagaaaggcgacccgctgatggtcacgga ggccatgaagatggagacgacgatcaccgcgccgattgccggcatcgtcaaggaggtctgtgtcgcagcaggcagc cgcatcacttccggcgacctcctcgctgtcatcgaataa 1141 AA PAT source 1..1141 mol_type protein organism unidentified

MKNIRKILVPNRGEIAIRIFRACHEMGIRTVAVYSKEDVLSLHRSRADEAYLVGKGKKPVDAYL

DIEDIIRICKEHDVDAIHPGYGFLSENAQLAKRCEDEGIIFIGPKVEHLQMFGDKVNARIQAER

ADIPMIPGTNGAVKDFAEVKAFAERVGLPIMIKAINGGGGRGMRRVDRMEDLKEAYDEARSE

AKRAFGDEDVYVEKCILNPKHIEVQIMGDEHGNVIHLNERDCSIQRRHQKVIEMAPAWSLPK

KLRQNICAAALKIMKNVHYVNAGTVEFLADQDEEHFYFIEVNPRVQVEHTVTEAITDIDIVKTQ

ILVAEGHALSDPEIGIKSQEDIPCNGVAIQCRITTEDPQNNFMPDTGKINDYRSGGGPGIRLDA

GTAYTGAVITPYYDSLLVKVTAHANNAPETIYRMLRCLDEFRIGGVKTNIYFLKNMLLDKNFQA

GSCNVNYIDHHPDLLNAPQVIDEPAAGLLAYIGEVTVNGFHGNGSNPKPRFETPVKLNAADEA

CPSGTRQLLEELGPEKFSKWIQDQKQVLLMDTTYRDAHQSLLATRIRTRDIMQAIHYTACKVP

QIYAFEDWGGATFDVAYRFLDEDPWERLRKMREAAPNILFQMLTRGANTVGYTNYPPEVVRQ

FLALAAKNGVDVFRIFDCLNQLDHMTLSIDEVRKQGKLAETAFCYTGDILDDGRQKYTLKYYT

NLAKEMEKAGANIIAIKDMAGLLKPEAAYTLISALKDAVDLPIHLHSHEGGGCTLYTYAKAAEA

GVDIVDVATSALSNGTSQPSMTAFIQALSNNPRQPQMDIEELETIDRYWQVVRAYYAGVDGK

MTSPNTTVFQHEMPGGQYTNLRQQAKGVGLGDRWPEVCRMYAKVNEMFGDVIKVTPSSKVV

GDMTLFMVQNNLTEKDIYERGETMDFPKSVVDFFDGKLGVPYGGFPEKLQKIILRGEQPHLET

PPAPIDQEKVTQDMKALRMPETEEARSSYCIYPKVYKDYIQRYHQYGDLSILDTPTYFFGMKPG

EESWLRIGGKMVLIRMNYITPPSDDGFREIQFEVNGMPREIRVRDKAASEGAAIIRQADPTVP

GEVAATLSGSVLRLIAAKGDVVKKGDPLMVTEAMKMETTITAPIAGIVKEVCVAAGSRITSGDL

LAVIE 969 DNA PAT source 1..969 mol_type unassigned DNA organism unidentified atgaaggtaacagttgttggtgcaggtaatgttggtgcaacggtcgcaaacgttcttgctacgaagaagttctgcagc gaggttgttcttgttgatatcaaggaaggcgttccgcagggcaaggccatggatatcatgcagacggctcacatgctg aactttgacacgacggtaacgggcgttacggctctgccgaacgatccggaaggctatgctccgacggctggttctgat gttgtcgttgtcacgtctggcatgccgcgcaaaccgggcatgagccgtgaggacctcatcggcgtcaacgctaagatc gtcaagagcgttgttgaccaggccctcaagtattccccgaatgcttacttcatcatcatctccaacccgatggacgctat gacgttcctgacgctcaaggacacgaagctcccgcgcaaccgcatcctcggccagggcggcatgctcgacagcagcc gtttccgttatttcctcgcacaggctctgacgaaggctggctatccggctacgccggctgacgttgatggcatggtcatc ggcggccacagcgacaagacgatggttccgctcgtcagctatgcaacgctgcgcggcatccctgtaacgcagctcctg agcaaggaagcactcgacgacgttgtcgctcagacgaaggtcggcggcgctacgctgacgaagctcctcggcacgt ccgcttggattgcaccgggcgctgcagctgctacgatggttgaagccatcgccctcgatgccaagaagctcatcccgt gctgcgtctacctcgaaggcgagtatggcgagaaggacctctgcatcggcgtaccgtgcatcctcggcaagaacggc ctcgagaagatcgtcgagatcaagctcgatggcgacgagaaggctaaattcgaagagagcgttcaggctgctcgca acacgaacgcaaaactcggcgatgccctcaaataa 322 AA PAT source 1..322 mol_type protein organism unidentified

MKVTVVGAGNVGATVANVLATKKFCSEVVLVDIKEGVPQGKAMDIMQTAHMLNFDTTVTGVT

ALPNDPEGYAPTAGSDVVVVTSGMPRKPGMSREDLIGVNAKIVKSVVDQALKYSPNAYFIIIS

NPMDAMTFLTLKDTKLPRNRILGQGGMLDSSRFRYFLAQALTKAGYPATPADVDGMVIGGHS

DKTMVPLVSYATLRGIPVTQLLSKEALDDVVAQTKVGGATLTKLLGTSAWIAPGAAAATMVEA

IALDAKKLIPCCVYLEGEYGEKDLCIGVPCILGKNGLEKIVEIKLDGDEKAKFEESVQAARNTNA

KLGDALK 1248 DNA PAT source 1..1248 mol_type unassigned DNA organism unidentified atgagcaaattgaacgaccaggcattggccctgcatagagaacaccacggcaagatcgagatgcacagcaaggtcc ccctccagaaggcgaaggacctgacgctggcctactcgccgggcgtcgctgcgccgtgcttggagattcagaaggac tacaacaagatctatgactacaccaacaagggcaacacggtcgccgtcgtgacgaacggcagcgctgtactcggcct cggcaacatcggcgctggcgccggcctgccggtcatggagggcaagtccatcctgttcaagggcttcgcaggcgtcg actccgtccccatctgcctcgacacgcaggacgtcgatgagattgtccgcgccgtcgagctcatggcgccgacattcg gcggcatcaacctcgaggacatcaaggcaccgcagtgctttgacatcgagaagcgcctgcagaaactcgatatcccg gtcttccacgacgaccagcacggcacggccatcgtcgtcgtctcggccctcatcaacgccttcaagctcacgggccgc aagttcgaggagtcgaagttcgtcctcaacggcgcaggtgccgctggccaggccatcacgcacctcatttacagcatg ggcggccgcaacatcatcctctgcgaccgcatgggtgccatctacgaaggccgcaaggaagacatgaacccctaca aggacgccatcgccaaaatcacgaacccgcagcatgaggcgggccagctcaaagacgtcatcaaggacgccgacg tcttcatcggtgtctccgtagccggtgcagtcacccaggacatggtccgctccatgaagaaggacccgatcgtcatgg gcatggccaacccgacgccggaaatcatgccggatgaggcctacgctgccggtgcccgcatcgtctgcacgggccgc agcgactacccgaatcaggtcaacaacctgctggccttcccgggcatcttccgcggcgctctcgacgtccgcgcgaaa aagatcaacgaagagatgaagatggctgccgccaaggccatcgccgacctcatcgacgagagcgaactcgatgag cagcacgtcatcacgagcccgttcgacccgcgcgtcgcaccgcacgtcgccgcagccgtagcagatgccgccatcaa gactggcgtcgcccgcatcaccgacatcacgcccgacgaggtagccgagcacacccgccagctcctcgccgccgagc acgccagcgaggcctga 415 AA PAT source 1..415 mol_type protein organism unidentified

MSKLNDQALALHREHHGKIEMHSKVPLQKAKDLTLAYSPGVAAPCLEIQKDYNKIYDYTNKGN

TVAVVTNGSAVLGLGNIGAGAGLPVMEGKSILFKGFAGVDSVPICLDTQDVDEIVRAVELMAP

TFGGINLEDIKAPQCFDIEKRLQKLDIPVFHDDQHGTAIVVVSALINAFKLTGRKFEESKFVLNG

AGAAGQAITHLIYSMGGRNIILCDRMGAIYEGRKEDMNPYKDAIAKITNPQHEAGQLKDVIKD

ADVFIGVSVAGAVTQDMVRSMKKDPIVMGMANPTPEIMPDEAYAAGARIVCTGRSDYPNQV

NNLLAFPGIFRGALDVRAKKINEEMKMAAAKAIADLIDESELDEQHVITSPFDPRVAPHVAAAV

ADAAIKTGVARITDITPDEVAEHTRQLLAAEHASEA 843 DNA PAT source 1..843 mol_type unassigned DNA organism unidentified ttgcgagaactcgacgcaaaacaaatcacggaaaccgttgcacagctgtgcaaggaggcggcttattacctgccgaa agatgtctatgagggcctcaagaagggccgcgagacggagaagtccccggttggccaggctgtactcgaccagatt atcaagaatgcggaaatcgcacgcgatgaggatcgcccgtactgccaggataccggcatgacgatcgtcttcctcga ggtaggccaggacctccacatcgtcggcggcgacctcgaagaggcagtcaacgacggtatcgccaagggctacacg gaaggctacctgagaaaatcggtcgttgcagagccaatcttcaaccgcgtcaacacccagaacaacacgccgggcgt catctacacgaagatcgttccgggcgacaagctcaagatcacggttgagccgaagggcttcggttccgagaacaagg gcggcatcaagatgctcgtaccggctgacggccttgagggcgtcaagaaggctgtcatggagatcatcctgcatgcc agcatgaacccgtgcccgccgatggtcgtcggcatcggtatcggcggcacgatggaccgcgccgctgtcatgagcaa gattgccctgacgcgttcgatcgactcgcataacccgatgccagaatatgcgaaactcgaagacgatctcctcgagct catcaatgaaacgggtattggaccgcagctcggcggcacgacgtcctgcctcggtgtcaacatcgagtggggcccga cgcacatcgccggcctgccggtcgctgtgacgatctgctgccatgcatgccgtcatgcaaagcgcgttctttga 280

AA PAT source 1..280 mol_type protein organism unidentified

MRELDAKQITETVAQLCKEAAYYLPKDVYEGLKKGRETEKSPVGQAVLDQIIKNAEIARDEDRP

YCQDTGMTIVFLEVGQDLHIVGGDLEEAVNDGIAKGYTEGYLRKSVVAEPIFNRVNTQNNTPG

VIYTKIVPGDKLKITVEPKGFGSENKGGIKMLVPADGLEGVKKAVMEIILHASMNPCPPMVVGI

GIGGTMDRAAVMSKIALTRSIDSHNPMPEYAKLEDDLLELINETGIGPQLGGTTSCLGVNIEW

GPTHIAGLPVAVTICCHACRHAKRVL 567 DNA PAT source 1..567 mol_type unassigned DNA organism unidentified atggcagaacctattcgcatccataccccgttcacggaagaagattcccacaagctcaagatcggcgacagcgttctc atcacgggcgagatctacgctgcacgcgatgctgcgcacaagaagatgtgcgaggcactcgctaaaggcgagaag ctgccgatcgactggcacaacaagatggtctattacctcggaccgactccggcaaaaccgggtgatccgatcggctcc tgcggcccgacgacttctggccgcatggatgcctacacgccgacgatgctcgagcagggcatcaagggcatgatcgg caagggctcccgttcgaaggaagtcgtcgattccatgaagaagaacggcgttacgtatttcgctgctgtcggcggtgc cgcagcgctcatcgcgaagtccgtcaagaagtacgaagttctcgcttacccagaactcggcccggaggcacttgcccg cctgaccgttgaggatttcccagctattgttgtcatcgactgcgaaggcaataacctttacgatgtcaaccaggagaag tatcgtaccctgaagggttactga 188 AA PAT source 1..188 mol_type protein organism unidentified

MAEPIRIHTPFTEEDSHKLKIGDSVLITGEIYAARDAAHKKMCEALAKGEKLPIDWHNKMVYYL

GPTPAKPGDPIGSCGPTTSGRMDAYTPTMLEQGIKGMIGKGSRSKEVVDSMKKNGVTYFAAV

GGAAALIAKSVKKYEVLAYPELGPEALARLTVEDFPAIVVIDCEGNNLYDVNQEKYRTLKGY

627 DNA PAT source 1..627 mol_type unassigned DNA organism unidentified atgttccatacaactttttatctgcgcegtctgcactcgttagtcggcctgctggcaatcggcattttcctcttcgagcatat cattacgaatgctcgtgcactcggcggtgctgagtccctcaacggtgctctggccatgatggagctcatcccgcatccg atcttcctcggcctggagatcttcggtgtcgcactgccgatcctcttccatgccatctacggcatctacatcgcccttcagg cgaagaacaacccgggccgctacggctacgtccgcaactggcagttcgctctgcagcgctggacggcatggttcctc gtcatcttcctcatctggcatgtgttctacctgcgcatcttcacgaaggccatcaacggcacgccgatctcgtatgagctg ctgcatacgctcttcacgagcagcccgatcacgacgctgctctacacgatcggcatgttcgcagctatcttccatttctgc aatggtatcacgactttctgcatgacctggggcatcgccaagggcccgcgcatccagaacgtcatcaacgttctctcga tgtgcctctgcgcattcctctgcettgtcacgattgcgttcatggcaagctactttgtcatgtaa 208 AA PAT source 1..208 mol_type protein organism unidentified

MFHTTFYLRRLHSLVGLLAIGIFLFEHIITNARALGGAESLNGALAMMELIPHPIFLGLEIFGVALP

ILFHAIYGIYIALQAKNNPGRYGYVRNWQFALQRWTAWFLVIFLIWHVFYLRIFTKAINGTPISY

ELLHTLFTSSPITTLLYTIGMFAAIFHFCNGITTFCMTWGIAKGPRIQNVINVLSMCLCAFLCLVT

IAFMASYFVM 1908 DNA PAT source 1..1908 mol_type unassigned DNA organism unidentified atggctaagaaaccagaaaataagattattgtcgtaggcggcggcctctcgggcectcatggctacgctgaagatctgce gaaggcggcggcaaggttgacctcttctcttactgcccggtcaagcgttcccactccctctgtgcacagggcggcatca acgcctgcatggacacgaagggtgagcatgactcgatctacgagcatttcgatgatacggtctacggcggcgacttcc tcgctgaccagctcgctgtcaagggcatggtcgaagctgcaccgaagctcatcaagatgttcgaccgcatgggcgtgc cgttcacgcgcacggctgaaggtgttctcgacctccgtaacttcggcggccagaagaacaagcgcacggtcttcgctg gctccacgacgggccagcagctcctctacgctctcgacgagcaggttcgccgttgggaagtaaagggcggcgtcaag aagtatgagttctgggaattcatcaagatcatcaagaacaaagagggcatctgccgcggtatcgtcgcgcagaacat gaactccaatgagatcgtctcgttcccggctgacgttgtcatcctcgcaacgggcggccctggccaggtatacggccgc tgcacggcttcgacgatctgcaacggttcggctgtttccgctgtttaccagcagggcgctgagctcggcaacccggagt tcctccagatccatccgacggctatcccgggttccgacaagaaccgcctgatgtccgaggcttgccgcggtgagggcg gccgcgtctgggtttaccgcaagaacccgcagacgggcgaaaaagagcgctggtacttcctcgaggatatgtacccg gcatacggcaacctcgtaccgcgtgacgttgcatcgcgtgccatctacaaggtcgtcgtccacatgggcctcggcatgc acaacccgaaccgcgtctacctcgacctctcgcacatcccggctgattacctcgagcgcaagctcggcggcatccttga gatgtacagcgacttcatgggccaggatccgcgcaaggtcccgatggagatcttcccgtcgatccactactcgatggg cggcatctgggtcgatcgcgagcatcacacgaacatcccgggcctcctcgcttccggcgagtgcgattaccagtacca cggcgcaaaccgcctcggtgcaaactcgctgctgtcggcaacgtactcgggcacgatttctggcccagagtccctgcg cctcgcacgcagcggcaagctcggctctgccctgacggcagaagagctcgaggctgcccgccaggagtgcgtcgca gagttcgacaagatccgcaacatgaacggcacggagaatgcgcataagctccatcatgagctcggcgacatcatgta caagtacgtctccatcgagcgcgacaacaacggcctcaaagaatgcgtcaaggaactcaaggaaatcctcaagcgct gggacaacatcggcgttacggaccacggcacttgggcaaaccaggaagcgatgttcgtccgccagctgcgcaacat gatcatctatgcgatggccatcacgcagtccgctctgcagcgtgacgagagccgcggtgctcatgcgaagatcgtcct gaagtccgattacgataagatggacgaccagctcaaggaagccctcacgaagaagtacggcaagttccacttcgac gctgagacgggccgtggcacgacggatgacggcaacgacgacctcgtattcttcgagcgcaacgataagaagttcat gcgcacgaccatcgttaccttcgaccaggagaaggaagagccggtcgtttcctaccgtgaattcgagcactctctcatc aagccgcgtctgcgcaactatgccgtagctaagaaagagtaa 635 AA PAT source 1..635 mol_type protein organism unidentified

MAKKPENKIIVVGGGLSGLMATLKICEGGGKVDLFSYCPVKRSHSLCAQGGINACMDTKGEH

DSIYEHFDDTVYGGDFLADQLAVKGMVEAAPKLIKMFDRMGVPFTRTAEGVLDLRNFGGQKN

KRTVFAGSTTGQQLLYALDEQVRRWEVKGGVKKYEFWEFIKIIKNKEGICRGIVAQNMNSNEI

VSFPADVVILATGGPGQVYGRCTASTICNGSAVSAVYQQGAELGNPEFLQIHPTAIPGSDKNR

LMSEACRGEGGRVWVYRKNPQTGEKERWYFLEDMYPAYGNLVPRDVASRAIYKVVVHMGLG

MHNPNRVYLDLSHIPADYLERKLGGILEMYSDFMGQDPRKVPMEIFPSIHYSMGGIWVDREH

HTNIPGLLASGECDYQYHGANRLGANSLLSATYSGTISGPESLRLARSGKLGSALTAEELEAAR

QECVAEFDKIRNMNGTENAHKLHHELGDIMYKYVSIERDNNGLKECVKELKEILKRWDNIGVT

DHGTWANQEAMFVRQLRNMIIYAMAITQSALQRDESRGAHAKIVLKSDYDKMDDQLKEALT

KKYGKFHFDAETGRGTTDDGNDDLVFFERNDKKFMRTTIVTFDQEKEEPVVSYREFEHSLIKP

RLRNYAVAKKE 753 DNA PAT source 1..753 mol_type unassigned DNA organism unidentified atggcagaacagaaaaaagtcagaatcatcgtcgagcgccaggacggcccgaaagagaagccgtacaaccagga gttcgagatcgactatcgtccgggcctcaacatcgttgctgccctgatggaaatccagaagaacccggtaacggtcga cggcaagaaagtcccgccagtgacgtgggaatgcaactgcctcgagaaagtctgcggcgcctgcatgatggtcatca acggcaaggctcgccaggcttgctgcacgctcgttgatacgctcaagcagccaatccacctgcagccggcccgcacgt tcccggtcatccgcgacctgctcatcgaccgctccgtcatgttcgagagcctcaagcgcatccacggctgggtcgaagt cgacggcacgtgggaggtcaaggatgctccgatccagaacccgtacacggcacagacggcctacgagatctcgcac tgcatgacctgcggctgctgcctcgaggcctgcccgaacgtcggcccgcagtccgacttcatcggaccggctccgacg gtacaggcttaccttttcaacctccatccgctcggaaagttcgacgctccgaagcgcctgaacgcactgatggagaag ggcggcatcacgagctgcggcaacagccagaactgtgtcgaagcttgcccgaagaacatcaagctgacgacgtatct cgcacagctcaaccgcgatgtcaacaagcaggccctgaagaatatcttcaatcactga 250 AA PAT source 1..250 mol_type protein organism unidentified

MAEQKKVRIIVERQDGPKEKPYNQEFEIDYRPGLNIVAALMEIQKNPVTVDGKKVPPVTWECN

CLEKVCGACMMVINGKARQACCTLVDTLKQPIHLQPARTFPVIRDLLIDRSVMFESLKRIHGW

VEVDGTWEVKDAPIQNPYTAQTAYEISHCMTCGCCLEACPNVGPQSDFIGPAPTVQAYLFNLH

PLGKFDAPKRLNALMEKGGITSCGNSQNCVEACPKNIKLTTYLAQLNRDVNKQALKNIFNH

435 DNA PAT source 1..435 mol_type unassigned DNA organism unidentified atggcgactatcaagctggagattgtctcaccggataaagtggtctacgagaatgacatcagcatgctgatcgtccgc tcgacgggcggtgagctcggcatcctgccgcaccatgccccgctcgtcgcgggtctcgtgccgcatgccatgcgcatc cgcctcggcgcagaccgcgatgagcagctcatcgcggttgcgggcggcttcatggaagtcacgccggagaagatca cggtcctcgcgacggctgctgagcagccaatcgacattgacatcaaccgcgcgaaggaggccatggcccgcgccaa ggcccgcatcgccgccttccatcagggcacgcctgagggcaaggacgtcgatatcgaccgcgccgaactcgcactgc gccgctcgagtgcgcgtctgcgcgcactcggctcgcaattcgaagaataa 144 AA PAT source 1..144 mol_type protein organism unidentified

MATIKLEIVSPDKVVYENDISMLIVRSTGGELGILPHHAPLVAGLVPHAMRIRLGADRDEQLIA

VAGGFMEVTPEKITVLATAAEQPIDIDINRAKEAMARAKARIAAFHQGTPEGKDVDIDRAELAL

RRSSARLRALGSQFEE 1413 DNA PAT source 1..1413 mol_type unassigned DNA organism unidentified ttggcaaaaggtaaagtcgtacaggtcatcggacctgtcgtagatattgaattcccggcgggcgagctgccggcaatc ctcaatgccgtcaccatcaagggcaagacgagcattgacatcgacctcgtcgtcgaggtcatgcagcatcttggcgac agcgtcacgcgctgcatcgccatgagctcgacggacggtctgacgcgcggcatggaagcagtcgacacgggcaacc cgatcatggtcccggttggcacggagtgcctcggccgcgtcttcaacgtactcggtcagacggttgaccacaacccgg ctcctgtcggcaacaaggagtcctggccgatccatcgcccggctccgaagttcgacgagcaggagacgagcgcgca ggtcctcgagacgggcatcaaggtcgtcgacctcatcgctccgtactccaagggcggcaagacgggcctcttcggcg gcgcaggcgtcggcaagacggtcctcatcatggagctcatccacaacatcgcgacggagcacggcggttactccgtc ttcgccggcgtcggcgagcgcacccgtgagggcaacgacctctggggcgagatgactgagtcgggcgtcatcgaca agacggcactcgtctacggccagatgaacgagccgccaggagcacgtatgcgcgtcgccctgacgggcctgacgat ggcagagtacttccgcgatgtccagcatcaggacgtgctgctcttcatcgacaacatcttccgcttcatccaggctggtt ctgaggtttcggcactgctcggccgcatgccgtcggccgtcggttatcagccgacgctgtccacggatatcggtgctct gcaggagcgcatcacctcgacgaagaatggttccatcacgtcggttcaggcagtctatgtcccggccgatgacctgac ggacccggcaccggctggtacgttcacgcacctcgatgccacgacggtcctctcgcgtcagatcgccgagctcggcat ctacccggccgtcgatccgctcgattcgacgagccgcatcctcaacgccgaagtcctcggcgaggagcattacgaagt tgcccgcggtgtccaggccgtgctccagaagtacaaggagctccaggacatcatcgccatcctcggcatggaagagc tctccgatgaggataagctgactgtctcgcgtgcgcgcaagatccagcgctttctctcgcagcccttcttcgtcgcagag gtgttcacgggttcgccgggcaagtacgtgccgctcaaggagacggtacgcggcttcaaggagatcctcgagggca agtacgatgacctgccggagaatgccttctacatggtcggcacgatcgatgaggcagtggagaaagcacggaagat caaagaagaggagggataa 470 AA PAT source 1..470 mol_type protein organism unidentified

MAKGKVVQVIGPVVDIEFPAGELPAILNAVTIKGKTSIDIDLVVEVMQHLGDSVTRCIAMSSTD

GLTRGMEAVDTGNPIMVPVGTECLGRVFNVLGQTVDHNPAPVGNKESWPIHRPAPKFDEQET

SAQVLETGIKVVDLIAPYSKGGKTGLFGGAGVGKTVLIMELIHNIATEHGGYSVFAGVGERTRE

GNDLWGEMTESGVIDKTALVYGQMNEPPGARMRVALTGLTMAEYFRDVQHQDVLLFIDNIFR

FIQAGSEVSALLGRMPSAVGYQPTLSTDIGALQERITSTKNGSITSVQAVYVPADDLTDPAPAG

TFTHLDATTVLSRQIAELGIYPAVDPLDSTSRILNAEVLGEEHYEVARGVQAVLQKYKELQDIIA

ILGMEELSDEDKLTVSRARKIQRFLSQPFFVAEVFTGSPGKYVPLKETVRGFKEILEGKYDDLPE

NAFYMVGTIDEAVEKARKIKEEEG 858 DNA PAT source 1..858 mol_type unassigned

DNA organism unidentified ttggctagtttacaggatattcgccatcgcatcaagagcgtaaagagtaccaagcagatcacgagtgccatgaacatg gtcgctacgagccgtctgcgccatgccaaagaggctgcaaccgcgaaccgtccctatgcacagaaggtcagcgaggt cgtccacgccatcgccaagaatgcaggcatggacttctcgcacccactgctcgagaagcacgaggatggcaggaag ctcgtcttcctgatcacctcggacaagggattggcaggtgcgtattcgtcgaatgcctgcaaggcggcagagaccctc atcgagaaagcggacgatacggacttcgtcatcgtcggccgcaagggcgtgggccacttcaagacccgcggccaca aggtcatcaaggagttcatcggcatcagcgagcacccgtcttctgaggcggcgcgggacatcgctctcgagctcatcc agctctacaagacgggcgagtaccgcgaggtcgacatggtctacacgaagttcgtctcggccatcagctgcgagccg aaatcgggggcgctgctccegttcgccccgctgaaggcagaggaccaggacgacctgaacgtcgagtacatctatga gccagatgccgctacggtgctcggtttcatgctgccgcagtatctcttcacggtcgtttatgcagcgcttctgcagtcggc agccagcgagctctcctcgcgcatgaacgcgatgagcaacgcgacggacaacgcagaagacctcatggataaactc aatctgcattacaacaaggtacgtcaggctggcattacccgtgagatcactgagattgtcggcggcgccgaagccctt aagtga 285 AA PAT source 1..285 mol_type protein organism unidentified

MASLQDIRHRIKSVKSTKQITSAMNMVATSRLRHAKEAATANRPYAQKVSEVVHAIAKNAGM

DFSHPLLEKHEDGRKLVFLITSDKGLAGAYSSNACKAAETLIEKADDTDFVIVGRKGVGHFKT

RGHKVIKEFIGISEHPSSEAARDIALELIQLYKTGEYREVDMVYTKFVSAISCEPKSGALLPFAPL

KAEDQDDLNVEYIYEPDAATVLGFMLPQYLFTVVYAALLQSAASELSSRMNAMSNATDNAEDL

MDKLNLHYNKVRQAGITREITEIVGGAEALK 1518 DNA PAT source 1..1518 mol_type unassigned DNA organism unidentified atgaaaatgaatccggaagaaataacggccatcatcaaggaccagatcaagaattacgatgtggacctcaatgttga tgatgttggttccgttatcgagatcggtgacggcatcgcacacatccatggcctcgacaaggctatggcgggcgagct gctcgatttcggcaatgatatttatggtctggtcctgaaccttgagcaggacaacgtcggtgccgttatcttaggcggcg agacgaaaatcaaagagggctcgcaggtcaagcgcacgggccgcatcatgcaggttcctgtcggtgaggccatgat cggccgcgtcgtcgatgccctcggccgtccaatcgacggcaagggcaagatcgagacgacggagacgcgtccggtc gagtacccggcaccgggcatcgcagaccgcaagccggtcaaggagccgctgcagacgggcatcaaggccatcgac gccctcgtaccgatcggccgcggccagcgcgagctcatcatcggtgaccgcggcatcggcaagacggccatcgccat cgacacgatcctcaaccagcacgaccagaactgcatctgcgtctacgtcgccatcggccagaaggcctcgacggtcg cgcgcgtcgtcaagacgctcgaagagcgcggcgccatggactacacgatcgtcgtcgctgctacggctgctgacagc tcgccgctgcagtacctcgcaccgtatgccggtgtcgctatggctgagcacttcatgtatcagggcaaggcctgcctct gcgtctacgatgacctcacgaagcacgcagctgcttaccgcgccatgtccctgctgctccgcagaccgccaggacgtg aagcatatccgggcgatgtcttctacttgcattcccgcctgctcgagcgcgcagcgaagctcaacgatgagctcggcg gcggctccatcacggctctgccgatcatcgagacgcaggccggcgacctctcggcctacatcccgacgaacgtcatct ccatcacggacggccagatcatgctcgagacggactccttctattctggtatccgcceggccatcaacgtcggcctctcc gtatcgcgtgtcggcggctcggctcagatcaaggccatgaagcaggtagcaggtaccctgcgcctcgacctcgcgca gtaccgcgagctcgcagcgttctcgcagttcgcctcggacctcgacaaggagacgaaggcacagctcgaccgcggta tccgcatggtcgagacgctgaagcagccgcagtacagcccgctgctcgtccaggaacaggtcatggtcatctacacg gccgccaagggctatcttgttgatatcccggtcgagaaggtcgtcgagttccagacggacttcctgaagttcatgcgca cgcagcatccggaagtcgcacagaagatcattgaccagaagaaactcgatgatgctctggagacggagctcaagaa cgcgatcgtggagttcaaggaaactgtaccgtataaaatggcgtaa 505 AA PAT source 1..505 mol_type protein organism unidentified

MKMNPEEITAIIKDQIKNYDVDLNVDDVGSVIEIGDGIAHIHGLDKAMAGELLDFGNDIYGLVL

NLEQDNVGAVILGGETKIKEGSQVKRTGRIMQVPVGEAMIGRVVDALGRPIDGKGKIETTETR

PVEYPAPGIADRKPVKEPLQTGIKAIDALVPIGRGQRELIIGDRGIGKTAIAIDTILNQHDQNCI

CVYVAIGQKASTVARVVKTLEERGAMDYTIVVAATAADSSPLQYLAPYAGVAMAEHFMYQGK

ACLCVYDDLTKHAAAYRAMSLLLRRPPGREAYPGDVFYLHSRLLERAAKLNDELGGGSITALPI

IETQAGDLSAYIPTNVISITDGQIMLETDSFYSGIRPAINVGLSVSRVGGSAQIKAMKQVAGTL

RLDLAQYRELAAFSQFASDLDKETKAQLDRGIRMVETLKQPQYSPLLVQEQVMVIYTAAKGYL

VDIPVEKVVEFQTDFLKFMRTQHPEVAQKIIDQKKLDDALETELKNAIVEFKETVPYKMA 543

DNA PAT source 1..543 mol_type unassigned DNA organism unidentified atgctaaacttacagcttgtacggaaatacgccaaggcaatcttcgagattgcgcaggaagaggaaaagctcgtgga gtatggcgatgaactcaaggctgcgcgcgagggcatcgagtccgtgccgcaggcgatggagttcttctccaatccgc aggttgatccgaagcagaagaaggagctcctgcagaaatgcttcaagaaagagctctcgaagaacgtgtaccatttc ctgctgctgctggtcgacaagcaccgcttcgtgctgttcccggcaatagtggatgagtaccgcgtgctctcgaatgaag ccaggggcatcctgatcgcggacgtgacgacggtcgcgcctgcctcgaagaagcagcagaaggccatcgcagaca aattggaacagataacgggcaagaaagtggagctccgcctccacgaggacaagtcccttatcggcggcgtcgtcgtc aagatcggtgaccgccgcatcgatggcagtgtcgctggccgtctcgagacgatgaagagaaaattactggctaacga gtga 180 AA PAT source 1..180 mol_type protein organism unidentified

MLNLQLVRKYAKAIFEIAQEEEKLVEYGDELKAAREGIESVPQAMEFFSNPQVDPKQKKELLQK

CFKKELSKNVYHFLLLLVDKHRFVLFPAIVDEYRVLSNEARGILIADVTTVAPASKKQQKATADK

LEQITGKKVELRLHEDKSLIGGVVVKIGDRRIDGSVAGRLETMKRKLLANE 504 DNA PAT source 1..504 mol_type unassigned DNA organism unidentified ttgatagatatcaatgccacattgatcgctcagatcttgaacttcttgatcttggctggtctccttcgcgctgttgcctataa accggtcgtgcggatgctcaaagctcgtcaggaccgcatccaggaaagcctcgacaaggcggatgcagatgctgag gaagcggacaagctcctggctgagtacaaggcaaaacttgcggaggcgaacgtcaaggcggagaacatcgtcctg atggccgagaagcgtgcaagtgaggagcgcgaggcaaagcgcgctgaagtcaagcgcgagattgaacagatgcg caaggcagcaaaggctgagatcgaccgtgagcgcgagcatgcggtccagcagctgcgcaccgagatgattacgctg tccatggcagccgccggtaagatcgttgctaagaacatggacaagtccgagaacgaagcgctgatctcggatttcgtc aaggaactcgacaaggacaagattggtgatctgccatgctaa 167 AA PAT source 1..167 mol_type protein organism unidentified

MIDINATLIAQILNFLILAGLLRAVAYKPVVRMLKARQDRIQESLDKADADAEEADKLLAEYKAK

LAEANVKAENIVLMAEKRASEEREAKRAEVKREIEQMRKAAKAEIDREREHAVQQLRTEMITL

SMAAAGKIVAKNMDKSENEALISDFVKELDKDKIGDLPC 252 DNA PAT source 1..252 mol_type unassigned DNA organism unidentified atggaaaacgcaatcatggtcgcagcagctctcgtaggtgcaggtctttgcatgggtttggctgcagtcggcgctggc ctcggtgatggtcttgtcacgagccgctttatcgaaggtatcacgcgtcagccggaagcacagagcaagctcttcacg aatacgctgatctccgtecggcctcatcgagtccatggcaatcatcgcaacggtcgttgccctgatcatgctctatgcgaa cccgctcatcaaataa 83 AA PAT source 1..83 mol_type protein organism unidentified

MENAIMVAAALVGAGLCMGLAAVGAGLGDGLVTSRFIEGITRQPEAQSKLFTNTLISVGLIES

MATIATVVALIMLYANPLIK 678 DNA PAT source 1..678 mol_type unassigned DNA organism unidentified atgcatgaaattggtgttcgcgaagtagtgcatttcgccgggttgacattcaactgggagaccctttgcatgacttggct cacgatggcgatcgtcatcctgatctcatggctggcaacgcggaacctcaagatgattccgacgggctggcagaatgt ggtggagatcctcgtctcgtggctcgacacgcaggtgagctccatgatgggcaagcggggactgttcctggcgccgtt catcatgtcgctgttcatgttcctgctgacgtcaaactggctgggactcatcccgacgttgtcttcgccgacgaatgactt gaacaccaccttggggctggcgctgctcgtcgtcgtactggtacacgtactgggtgtccacatgaagggcggtcattat atcgcgcatttcttcaagccgacgccggtatttgtcatcatcaacgcgatcgaagagattgccaagccaatcacgctgt cgttccgtctattcggcaacatcctagcaggtgagatcttgatcatcatcctgctcaagctgatgccaatctggatgccg atcccgtcagtcatctggctggcattcagtatctttgteggcggagtccaggcgttcatcttcacgatgctgtcgatggct taccttgcgaatgcagtcaaggaagatgaagaagagtcgtga 225 AA PAT source 1..225 mol_type protein organism unidentified

MHEIGVREVVHFAGLTFNWETLCMTWLTMAIVILISWLATRNLKMIPTGWQNVVEILVSWLDT

QVSSMMGKRGLFLAPFIMSLFMFLLTSNWLGLIPTLSSPTNDLNTTLGLALLVVVLVHVLGVHM

KGGHYIAHFFKPTPVFVIINAIEEIAKPITLSFRLFGNILAGEILIIILLKLMPIWMPIPSVIWLAFSI

FVGGVQAFIFTMLSMAYLANAVKEDEEES 372 DNA PAT source 1..372 mol_type unassigned DNA organism unidentified atgaaacagattttatcggtcttcatgaagcgtctcgcgattgcccttgggcttgcggcgctgatgatcggcagccttct gctcgcgagaggagaagggcagctcatcggcgcactcttcctcggctatttcgcggcgctggtatttgtctggaacatg gcctggcgcctctggcgcctgacgtacatgcagagtggcggcaagaggcagatgctctggggcatggtgctccggat gctcgtgctcttcctegtcctgctcgtecgcggtgacgatctccgtaccggtattcctcgtcacggcgctcggttttctcgtct gctatggactcgccctgttcctgctgatccacatgaacctcggtaaaaaataa 123 AA PAT source 1..123 mol_type protein organism unidentified

MKQILSVFMKRLAIALGLAALMIGSLLLARGEGQLIGALFLGYFAALVFVWNMAWRLWRLTYM

QSGGKRQMLWGMVLRMLVLFLVLLVAVTISVPVFLVTALGFLVCYGLALFLLIHMNLGKK

1308 DNA PAT source 1..1308 mol_type unassigned DNA organism unidentified gtgaatttacaaatcttagtcttagtcctggcgattgtcctgtttggagttctggcatttaaacagatgagcgctttgatcc tggctccgcttgtcacgatctttgttgtcatctgctcgaaactcccaattctggactcgttaaaaaatgcgttcatgcctgc agcgtccgactacgtgacaaagtatttccttgtcttctttgteggcgcactgtttggttctgtttaccagtatactggagcc gcagaatccattgccagagccatcgcaggtctctgccgcggaaagttcgtggcaccgatcatcatgatcatcaccggt cttttgacctttggaggagtcagtggctttgttgtattctttgttatctatccgatcgctctgaacttatttaaagaggcgaa ccttacgagaaggcttatcccggctgcaatctctgccggatgctggacctggtccatgagcggccctggttctccttcca ttcagaacgttattgctatggataaccttggtacaccggcaactgccgcatttgttccatctctgatcacaacggttgcta tgtttttaatgatctttgtatggctggaaatgcgcgcaagaaagtttacaaaaaagggataccgctttattgacaaatct ttaaagtatcaattaagtgaagaggagacggcaattgatgaaaacaaagatcttcctcatgttgccatcgctatccttc cgatcattgtaatcctggtactctttaacattgtaaagctgccggtagagacatccgtatttgcaggcgtggctctggcta cagttctgatgttcaagagagtcaaaggcatcaacgaatggatcaatgtctttaacaaaggggcatctgattccggtgt cgctatcctgaatactgccattgtcgtaggattcggcggcgttgtgcagaaaacacaggggtttacagatctggtcgct gctctcaaagatatgagcatgccgcctctggtatttgtaatgatcactgtggctgtctgtgcaggagcctgcggttccgc ttccggcgggatgggcgttgccttcaatgcactgaagtctacctatatcaagatgggaattcctctgccttatgtacata ggatttccgcaattgccgctggtacattggatacccttcctcaccagggagcgcagatcactctgctcggcatttgtaaa atgacccataaggaagcctactgggatattgcggttacgcagattatcataccatttatatcctgcggaatctttatcgtt ttagcttcttttggactataa 435 AA PAT source 1..435 mol_type protein organism unidentified

MNLQILVLVLAIVLFGVLAFKQMSALILAPLVTIFVVICSKLPILDSLKNAFMPAASDYVTKYFLV

FFVGALFGSVYQYTGAAESIARAIAGLCRGKFVAPIIMIITGLLTFGGVSGFVVFFVIYPIALNLF

KEANLTRRLIPAAISAGCWTWSMSGPGSPSIQNVIAMDNLGTPATAAFVPSLITTVAMFLMIFV

WLEMRARKFTKKGYRFIDKSLKYQLSEEETAIDENKDLPHVAIAILPIIVILVLFNIVKLPVETSV

FAGVALATVLMFKRVKGINEWINVFNKGASDSGVAILNTAIVVGFGGVVQKTQGFTDLVAALK

DMSMPPLVFVMITVAVCAGACGSASGGMGVAFNALKSTYIKMGIPLPYVHRISAIAAGTLDTL

PHQGAQITLLGICKMTHKEAYWDIAVTQIIIPFISCGIFIVLASFGL 1560 DNA PAT source 1..1560 mol_type unassigned DNA organism unidentified atgggaaaagttaaaattatcacagcagatcaggctgctgccctggtggaggatcatacaacgatcacaaccagcgg atttgttgccagcggaatgccggaagctctcacaaaagctttggaaaaaagattcaaagaaaccggatcccccaaaa acctgactttgttttatgctgccgcccagggaaaccgtgacggaagcggcgcggatcattttgcccatgaaggtatgac aaaacgtgtcataggcggacattggaacatggttcctgcactgggacagatggttctggacaataaaatcgaaggct ataatctgcctcagggaacactggcacagttataccgtgccatcgcaggtcacaaacccggcgttatcagtcatgtag gattaaatacatttgctgacccacgcattgagggcggtaaattaaatgacattacaaccgaagatatcgtcgatgtagt tgaaatcctgggagaagagaaattattgtacaaatcgttcccgatcaacatcggatttatccgcggtacatatgcagat gaacacggcaacgtaactctgtctcacgaatgtgccaccacagaggtcacaaccatggctcaggccgtaaagaaca gcggcggaaaggtcgttgtacaggtagaaaaggtcgtttcagacggcaccttagatccaaaattagtcaagatccct ggaatttatgtggatgccgttgtggaagtagaagacatgaaggatcacgaacaatgcgtgggctgtgattatgatggt tccatgaccggagacttccgggttccgttaagcagtcttgagtacccgcctctttccgccaagaagatcattggacgca gagcagccatggaactgacagaaaacacggttgtaaatctaggcattggtattccagagtacatctccatggtagcca acgaagaaggcattggagattacatgactctgactgtagaggccggaccaatcggcggtgtacctcagggaggagc taaattcggaggcgctgtcaatgctgaatgtatcctagatcagccgtaccagtttgatttctatgacggcggcggagtt gactatgcattcttaggactcgcacaggcagataaagacggtaatatcaacgtaagcaagttcggtccaaggattgcg ggctgcggcggtttcgtcaatatcacccagaacgcaaaacgctgctacttctgcggaacttttactgcaggaggtctga agacatccgtaaaagacgggaaacttatcattgaccaggaaggaaaatcaaacaaattcctggataccgtagaaca gatcaccttcagcggtgaatacgcaaataaagtcggccagccggttctctatatcacagaacgtgctgtattcgaactc agaaaggacggcgtctatctgacagaggttgcccctggtatcgatatccagacacagatcatcgatcatatgggattt gctccaaagatggaaggaacgccaaagttcatggatgaaagaatcttcaaagatgagctgatgggcctgaagcacg attaa 519 AA PAT source 1..519 mol_type protein organism unidentified

MGKVKIITADQAAALVEDHTTITTSGFVASGMPEALTKALEKRFKETGSPKNLTLFYAAAQGNR

DGSGADHFAHEGMTKRVIGGHWNMVPALGQMVLDNKIEGYNLPQGTLAQLYRAIAGHKPGV

ISHVGLNTFADPRIEGGKLNDITTEDIVDVVEILGEEKLLYKSFPINIGFIRGTYADEHGNVTLS

HECATTEVTTMAQAVKNSGGKVVVQVEKVVSDGTLDPKLVKIPGIYVDAVVEVEDMKDHEQC

VGCDYDGSMTGDFRVPLSSLEYPPLSAKKIIGRRAAMELTENTVVNLGIGIPEYISMVANEEGI

GDYMTLTVEAGPIGGVPQGGAKFGGAVNAECILDQPYQFDFYDGGGVDYAFLGLAQADKDG

NINVSKFGPRIAGCGGFVNITQNAKRCYFCGTFTAGGLKTSVKDGKLIIDQEGKSNKFLDTVE

QITFSGEYANKVGQPVLYITERAVFELRKDGVYLTEVAPGIDIQTQIIDHMGFAPKMEGTPKFM

DERIFKDELMGLKHD 777 DNA PAT source 1..777 mol_type unassigned DNA organism unidentified atgaacaatttattaatggaagtagaaaacgaagtcgcagttgtaacaatcaacagaccaaaatcattaaacgcttta aacagtgaaactttagctgagttagaccagtgctttacagagatttcaggacgcaaggacatcagagtggtgatcctc acaggatcaggcgaaaaatcctttgtagctggtgctgatatctctgaaatggtcaatgcaactcctgcagaaggaaga cagatgggtcttttggcaaaagaagcatttcttaagttagagacaatgcctcaggtaaccatcgctgccgtcaacggtt acgctctgggaggcggatgcgagatctccatggcatgtgatatccgtgtagctgcggaaaacgcaaaattcgcacag ccagaaacaggacttggaattcttccgggattcggcggaacacagcgtctctcccgtttagtaggaaaaggacgcgc aaaggaattgatctttacatgtgaccagatcgatgccgaagaagcttacagaattggtcttgcaaacaaagtagtgcc tcaggcggagctgatcgattactgtaagaagatggctgcaaagatcatgtccaaaggaagctacgcaatttcccttgc aaaagaagcgatcaacacaggaatggacacagacttaagcagcggtcttacattagaagctgacttattcggacttg cattctccactgctgacaaaaaagagggtatgacagcattccttgaaaaacgtaaagctgatttaaaagatttctag 258 AA PAT source 1..258 mol_type protein organism unidentified

MNNLLMEVENEVAVVTINRPKSLNALNSETLAELDQCFTEISGRKDIRVVILTGSGEKSFVAGA

DISEMVNATPAEGRQMGLLAKEAFLKLETMPQVTIAAVNGYALGGGCEISMACDIRVAAENAK

FAQPETGLGILPGFGGTQRLSRLVGKGRAKELIFTCDQIDAEEAYRIGLANKVVPQAELIDYCK

KMAAKIMSKGSYAISLAKEAINTGMDTDLSSGLTLEADLFGLAFSTADKKEGMTAFLEKRKAD

LKDF 747 DNA PAT source 1..747 mol_type unassigned DNA organism unidentified atgagaattttggtttatttaaaagaaataccgccggaagaagaacgggatctgtaccaggatacagaggggatcaa tgacagtgatcagaatgtcttaatggaggcactgaatctgagggacaaggaaggcggaactgtgacggtcatggtc atcgggccgtccacaggagagaagacagcaagggaggcgctgacctggggagttgacaggtcagtcctggttttaa aggatggaaaggctacaggggatatcctggaaagtgcaagagtgctagcaaaagccatagaagcggaaggcaca tttgatgtaattttgtgcggaagacaggcgatagatggagatgcggcccatatggcggctatgacggcgtcctttttaa atatcccgcttattgccttctccaaaaaaatggagatctcggacggaaagctgtacaactggtgtatgtccaaagatgg gacagaacggacagagtgttgtatgccagcactggtcctctcagtgaaggaagacaacaaacgaaggcaccccaat gtctgtgatattatgtcagcttatgccgggagcactgtgatcccggttataaaaccagagagaaatacaccggagaag atcattagacaggttgggcagtatacgcccggcaaaaaacacaagaagggaatgatgctggccggaaaagatgaa caggaactggcgggacaactccggcagatattaacgaagttcacggcagcaaaatag 248 AA PAT source 1..248 mol_type protein organism unidentified

MRILVYLKEIPPEEERDLYQDTEGINDSDQNVLMEALNLRDKEGGTVTVMVIGPSTGEKTARE

ALTWGVDRSVLVLKDGKATGDILESARVLAKAIEAEGTFDVILCGRQAIDGDAAHMAAMTAS

FLNIPLIAFSKKMEISDGKLYNWCMSKDGTERTECCMPALVLSVKEDNKRRHPNVCDIMSAYA

GSTVIPVIKPERNTPEKIIRQVGQYTPGKKHKKGMMLAGKDEQELAGQLRQILTKFTAAK 981

DNA PAT source 1..981 mol_type unassigned DNA organism unidentified atggaaagagtatcaaagattttgattattggagaaatacaaaatggacagccagccccggtaactctggaattatta ggggagggagagaagatagcctcttctctgaacgcaaagcttttactggctgtagcgggcagcggtattcaggagat cttaagtgagcttttgcagtatcctgtagacaggatcattgcagtggatcatcccaggatggaattggatcaaacggag acccacgccagagttttggaggccgtgatccgggagcacgagccggatatgattctgggaggagcaacgttgtcag gaaaggtgctgctgccaatgctggctgcggttcttggaacagaagtggtgacagacgcggctgacctggagattgac aaggaaacagggaaacttctgatcagcaagccggcgtttgacggaaaaagaatgtctatagtatcgatgccaaagg cccacgtacagatcgtttctgtaaagcccgggatttttgagaaggcctgcaggacggaaagaaaaagaggcggtatc accatggtggcggctgactggctggaagatatcaaagagcggaaaaagatgctggagctgatcacagaagacggc aacaagatatctctggaagattcaaagatcatcgcagccggcggacggggactgaaagggcctgaaggatttgaac tccttacacggtttgcaagagaaatcggtgcccaggtgggctgcacaagaccatgtgtggatgcaggatggacctcg ccggagcagcagatcggccagaccggattcacaaccaaaccggatctctatctggcttttgggatttccggtgcgatcc agcatatgaccggagtccgggcaaagaccgtgatcgcagtcaataacaatccaaatgcggcaatttttaattattgcg actatgggatcgtcggggatgcccaaaaaatattgagagaactactaagagaatag 326 AA PAT source 1..326 mol_type protein organism unidentified

MERVSKILIIGEIQNGQPAPVTLELLGEGEKIASSLNAKLLLAVAGSGIQEILSELLQYPVDRIIA

VDHPRMELDQTETHARVLEAVIREHEPDMILGGATLSGKVLLPMLAAVLGTEVVTDAADLEID

KETGKLLISKPAFDGKRMSIVSMPKAHVQIVSVKPGIFEKACRTERKRGGITMVAADWLEDIK

ERKKMLELITEDGNKISLEDSKIIAAGGRGLKGPEGFELLTRFAREIGAQVGCTRPCVDAGWT

SPEQQIGQTGFTTKPDLYLAFGISGAIQHMTGVRAKTVIAVNNNPNAAIFNYCDYGIVGDAQKI

LRELLRE 1143 DNA PAT source 1..1143 mol_type unassigned DNA organism unidentified atgaattttgaattaacagagcagcaggcagccattcaggaaacagcaaggaactttgctcagacagaactgcagcc aggtgtgctggagagagatgcaaacagtgagtttccggtagatctttataagaagatgggggatatgggcctgatcg gtcttccatatccgaaagaagtcggaggacagggagccgattatctttcttatgcactggcagtggaagagatctcaa aagtagatgcctctgtgggtatttcctattctgtttccacctctctgtatggcggaagcattatgaactctgatgcttccgtt gagaaaaagaatgaatttctagcaccggtactgtccggacagcatttcggatcctttggactcacagagcccaatgcc ggatcagacgcaggcggatgtgtcactgtggctgaaaaagatggggacgaatacatattaaatggtatgaagtgttt taacaccaacggacctttggccgattatacagcggtatatgccctgacagaacctgagaagaaagcaaagggtctttc ctgctttgtagtaaaaaaaggaactcctggattttctgtaggcaaggtggaggataagatgggaatccgctctgcgca ggtctctgagatgatcctggaaaatgtcagagtacctgcagagaatatggtcgttccatctggggacggatttaagct ggccatgaagactttggatggaggacgcatcggcgttgccgcgcaggggcttggtatcgcggagggcgcatttgag atcgcaaaagaatacttaaagagcagagaacagttcggcaaaccattatataaaaaccagtatcttgcatttaagatg gcggaacttgaaatggagatcgacgctgcaagatacatgctttacaaagcggctacagataaacacgagggaagat cttactcaatcccggcagcaaaggcaaaatacctttgtacagaggccgctatgcatgtgacaacagaagcagtacag atgttaggtggaaatgggtatatgaagggttaccatgtagaacgtatgatgagagatgcgaagatcactcagatctat gagggaaccaatgaaatccagaagctcgttgtaagcggagctatcttcagatag 380 AA PAT source 1..380 mol_type protein organism unidentified

MNFELTEQQAAIQETARNFAQTELQPGVLERDANSEFPVDLYKKMGDMGLIGLPYPKEVGGQ

GADYLSYALAVEEISKVDASVGISYSVSTSLYGGSIMNSDASVEKKNEFLAPVLSGQHFGSFG

LTEPNAGSDAGGCVTVAEKDGDEYILNGMKCFNTNGPLADYTAVYALTEPEKKAKGLSCFVVK

KGTPGFSVGKVEDKMGIRSAQVSEMILENVRVPAENMVVPSGDGFKLAMKTLDGGRIGVAA

QGLGIAEGAFEIAKEYLKSREQFGKPLYKNQYLAFKMAELEMEIDAARYMLYKAATDKHEGRS

YSIPAAKAKYLCTEAAMHVTTEAVQMLGGNGYMKGYHVERMMRDAKITQIYEGTNEIQKLVV

SGAIFR 1350 DNA PAT source 1..1350 mol_type unassigned DNA organism unidentified tttgagagtcgagtggcaaacgggtgagtaacgcgtagacacctgccgtaaagatggggacaacagttcgaaagga ctgctaataccgaatgttgtagagtttccgcatgggaatcctactaaaggtggcctctacttgtaagctatcgctttacga tgggtctgcgtctgattagctagttggtggggtaacggcctaccaaggcgacgatcagtagccggtctgagaggatg aacggccacattggaactgagacacggtccagactcctacgggaggcagcagtggggaatcttccgcaatgggcgc aagcctgacggagcaacgccgcgtgagtgaagaagggtttcgactcgtaaagctctgttgtcggggacgaatgtgg agatggtgaataaccattttcaatgacggtacctgacgaggaagccacggctaactacgtgccagcagccgcggtaa tacgtaggtggcgagcgttgtccggaattattgggcgtaaagggagcgcaggcgggaaggtaagtctatcttaaaag tgcggggctcaaccccgtgaggggatggaaactatctttcttgagtgcaggagaggaaagcggaattcctagtgtag cggtgaaatgcgtagatattaggaggaacaccagtggcgaaggcggctttctggactgtaactgacgctgaggctcg aaagcgtggggagcgaacaggattagataccctggtagtccacgccgtaaacgatgaatgctaggtgtaggaggta tcgacccctcctgtgccggagttaacgcaataagcattccgcctggggagtacggccgcaaggctgaaactcagagg aattgacgggggcccgcacaagcggtggagtatgtggtttaattcgacgcaacgcgaagaaccttaccagggcttga cattgagtgaaaggactagagatagtcccctctcttcggagacacgaaaacaggtggtgcatggctgtcgtcagctcg tgtcgtgagatgttgggttaagtcccgcaacgagcgcaacccctatcctttgttgccagcacgcaatggtgggaactca aaggagactgccgcggacaacgcggaggaaggcggggatgacgtcaagtcatcatgccccttatgtcctgggctac acacgtactacaatgggatggacagagagcagcgaagccgcgaggccaagcgaaccccataaaccatctcccagtt cggattgcaggctgcaacccgcctgcatgaagttggaatcgctagtaatcgcaggtcagcatactgcggtgaatacgt tcccgggccttgtacacaccgcccgtcacaccacggaag 1382 DNA PAT source 1..1382 mol_type unassigned DNA organism unidentified tattttggattgaagttttcggatggatctccttaatgactgagtggcggacgggtgagtaacgcgtggggaacctgcc ctatacagggggataacagctggaaacggctgctaataccgcataagcgcacagaatcgcatgattcagtgtgaaa agccctggcagtataggatggtcccgcgtctgattagctggttggcggggtaacggcccaccaaggcgacgatcagt agccggcttgagagagtggacggccacattgggactgagacacggcccaaactcctacgggaggcagcagtgggg aatattgcacaatgggggaaaccctgatgcagcgacgccgcgtgagtgaagaagtatttcggtatgtaaagctctatc agcagggaagaaataagacggtacctgactaagaagccccggctaactacgtgccagcagccgcggtaatacgta gggggcaagcgttatccggaattactgggtgtaaagggtgcgtaggtggcatgataagtcagaagtgaaagcccgg ggcttaaccccgggactgcttttgaaactgtaatgctagagtgcaggagaggtaagcggaattcctagtgtagcggtg aaatgcgtagatattaggaggaacaccagtggcgaaggcggcttactggactgtcactgacactgaggcacgaaag cgtggggagcaaacaggattagataccctggtagtcnacgccgtaaacgatgaatactaggtgtcggggccgtaga ggcttcggtgccgcagcaaacgcagtaagtattccacctggggagtacgttcgcaagaatgaaactcaaaggaattg acggggacccgcacaagcggtggagcatgtggtttaattcgaagcaacgcgaagaaccttacctggtcttgacatcct tctgaccggttnnnaaccgaacctttccttcgggacagaagtgacaggtggtgcatggttgtcgtcagctcgtgtcgtg agatgttgggttaagtcccgcaacgagcgcaacccctatctttagtagccagcatataaggtgggcactctagagaga ctgccagggataacctggaggaaggtggggacgacgtcaaatcatcatgccccttatggccagggctacacacgtgc tacaatggcgtaaacaaagggaagcgaccccgcgagggcaagcaaatcccagaaataacgtctcagttcggattgt agtctgcaactcgactacatgaagctggaatcgctagtaatcgtgaatcagaatgtcacggtgaatacgttcccgggt cttgtacacaccgcccgtcacaccatgggagtcagtaacgcccgaagtcagtgacccaaccgcaaggaggaga 258 DNA PAT source 1..258 mol_type unassigned DNA organism unidentified atggacgagaaaaacaaggacacgacgcatgagatgctgcgcacgggcctgcgccaggccatcaaggctttcgctg tcttgagtggcgtcggcatctacctcgccgtcettcgtcggcatctgtctgttcctcgggaatctggcggacacgtatctctt gggcggcggctatgcaggcaagctcacgggcatcctcgtcggettccccggegccttctacaccctgttccgtcagctc aagcagaacgggattgtctga 85 AA PAT source 1..85 mol_type protein organism unidentified

MDEKNKDTTHEMLRTGLRQAIKAFAVLSGVGIYLAVFVGICLFLGNLADTYLLGGGYAGKLTGI

LVGFPGAFYTLFRQLKQNGIV

Claims

CONCLUSIONS

1. Bacterium comprising a gene set enabling the bacterium to convert phytate into 3-hydroxypropionate or a salt or ester thereof, for use in the prevention and/or treatment of metabolic syndrome, insulin resistance, insulin resistance-related disorders or obesity, wherein the gene set comprises genes encoding the proteins: phytase, major myo-inositol transporter lolT, myo-inositol 2-dehydrogenase, inosose dehydratase, 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase, 5-deoxyglucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2-deoxy-D-gluconate-6-phosphate aldolase, 2-hydroxy-3-oxopropionate reductase and D-beta-hydroxypropionate permease.

A bacterium for use according to claim 1, wherein the bacterium is in association with a second bacterium comprising a gene set enabling the second bacterium to convert 3-hydroxypropionate or a salt or ester thereof into propionate or a salt or ester thereof, wherein the gene set of said second bacterium comprises genes encoding one or more of the proteins: permease, oxoacid-CoA transferase, dehydratase, electron transfer flavoprotein beta subunit, electron transfer flavoprotein alpha subunit and acyl dehydrogenase.

A composition for use in preventing and/or treating metabolic syndrome, insulin resistance, insulin resistance-related disorders or obesity, the composition being obtainable by: a) culturing a bacterium as defined in claim 1 and optionally a bacterium as defined in claim 2 in a suitable aqueous medium; b) separating the bacterium as defined in claim 1 and optionally the bacterium as defined in claim 2 from the aqueous medium to thereby obtain the composition.

A bacterium for use or a composition for use according to any preceding claim, wherein the bacterium defined in claim 1 is a Mitsuokella species, preferably Mitsuokella jalaludinii or a relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity to SEQ ID NO:93 and/or wherein the bacterium defined in claim 2 is an Anaerostipes species, preferably Anaerostipes rhamnosivorans or a relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity to SEQ ID NO:94.

A bacterium for use or a composition for use according to any one of the preceding claims, wherein the bacterium defined in claim 1 is Mitsuokella jalaludinii, as deposited under deposit number CBS150836; and/or wherein the bacterium defined in claim 2 is Anaerostipes rhamnosivorans, as deposited under deposit number CBS 140182.

6. A bacterium for use or a composition for use according to any preceding claim, wherein the bacterium or composition is not present in feces.

7. A bacterium for use according to any preceding claim, wherein the use consists of preventing and/or treating insulin resistance or an insulin resistance-related condition.

Bacterium for use according to any one of the preceding claims, wherein the insulin resistance related condition is selected from dyslipidemia, (metabolic) adenylosuccinate lyase deficiency ((M)ASLD) / (metabolic) dysfunction-associated steatohepatitis ((M)ASH), diabetes mellitus type 2 and insulin resistance in endocrine diseases.

9. A bacterium for use according to any preceding claim, wherein the bacterium is a human intestinal isolate bacterium.

10. A bacterium for use according to any preceding claim, wherein the bacterium is comprised in a composition further comprising a physiologically acceptable carrier.

A bacterium for use according to claim 10, wherein the composition is a food composition, preferably a dairy product, more preferably a fermented dairy product, such as yoghurt or yoghurt drink, or the composition is a pharmaceutical composition, preferably in solid dosage form, such as a capsule, a tablet or a powder.

12. A bacterium for use according to claim 10 or 11, wherein the bacterium is present in the composition in lyophilised or microencapsulated form.

A bacterium for use according to any preceding claim, wherein the bacterium is present in an amount within the range of 108 to 1015 colony forming units (CFU).

A bacterium for use according to any preceding claim, wherein the bacterium is administered separately, sequentially or simultaneously with phytate.

15. Bacteria for use according to any of the preceding claims for use as a probiotic.