CN108660093B - A kind of marine streptomyces, tunicamycin compounds and preparation method thereof - Google Patents
A kind of marine streptomyces, tunicamycin compounds and preparation method thereof Download PDFInfo
- Publication number
- CN108660093B CN108660093B CN201810481038.3A CN201810481038A CN108660093B CN 108660093 B CN108660093 B CN 108660093B CN 201810481038 A CN201810481038 A CN 201810481038A CN 108660093 B CN108660093 B CN 108660093B
- Authority
- CN
- China
- Prior art keywords
- tunicamycin
- streptomyces
- scsio
- preparation
- extract
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical class O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 241000187747 Streptomyces Species 0.000 title abstract description 24
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 claims abstract description 43
- YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000000855 fermentation Methods 0.000 claims abstract description 34
- 230000004151 fermentation Effects 0.000 claims abstract description 34
- 241000187180 Streptomyces sp. Species 0.000 claims abstract description 23
- 239000000284 extract Substances 0.000 claims description 16
- 238000011218 seed culture Methods 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 239000001963 growth medium Substances 0.000 claims description 14
- 241000193388 Bacillus thuringiensis Species 0.000 claims description 13
- 241000222122 Candida albicans Species 0.000 claims description 13
- 229940097012 bacillus thuringiensis Drugs 0.000 claims description 13
- 229940095731 candida albicans Drugs 0.000 claims description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 12
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 claims description 10
- 239000003242 anti bacterial agent Substances 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 241001587868 Streptomyces marinus Species 0.000 claims description 7
- 239000006228 supernatant Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 235000002639 sodium chloride Nutrition 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 229940041514 candida albicans extract Drugs 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 239000012138 yeast extract Substances 0.000 claims description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 238000010828 elution Methods 0.000 claims description 2
- 238000002386 leaching Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000009629 microbiological culture Methods 0.000 abstract description 2
- 229940125904 compound 1 Drugs 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 108020004465 16S ribosomal RNA Proteins 0.000 description 3
- 241000186361 Actinobacteria <class> Species 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 229930000044 secondary metabolite Natural products 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- -1 tunicamycin compound Chemical class 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 241001655322 Streptomycetales Species 0.000 description 2
- 229940124350 antibacterial drug Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 239000002028 Biomass Substances 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000195585 Chlamydomonas Species 0.000 description 1
- 241000186650 Clavibacter Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 101000775692 Pseudopleuronectes americanus Ice-structuring protein 4 Proteins 0.000 description 1
- 241001467568 Rathayibacter rathayi Species 0.000 description 1
- 241000187130 Streptomyces chartreusis Species 0.000 description 1
- 241001036087 Streptomyces xinghaiensis Species 0.000 description 1
- 241001036093 Streptomyces xinghaiensis S187 Species 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 229940042040 innovative drug Drugs 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- UOZODPSAJZTQNH-LSWIJEOBSA-N paromomycin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO UOZODPSAJZTQNH-LSWIJEOBSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-O vancomycin(1+) Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C([O-])=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)[NH2+]C)[C@H]1C[C@](C)([NH3+])[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-O 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/465—Streptomyces
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
- C07H13/06—Fatty acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/38—Nucleosides
- C12P19/385—Pyrimidine nucleosides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明公开了一种海洋链霉菌、衣霉素类化合物及其制备方法。海洋链霉菌(Streptomyces sp.)SCSIO 15077于2017年1月23日保藏于中国微生物菌种保藏管理委员会普通微生物中心(CGMCC)，地址：北京市朝阳区北辰西路1号院3号，中国科学院微生物研究所，保藏编号为：CGMCC No.13649。本发明的海洋链霉菌(Streptomyces sp.)SCSIO 15077的发酵培养物能够制备新化合物衣霉素E，如式(I)所示。本发明为衣霉素的生产制备提供了生物制备方法，具有广阔的应用前景。
The invention discloses a marine streptomyces and tunicamycin compounds and a preparation method thereof. Streptomyces sp. SCSIO 15077 was deposited on January 23, 2017 in the General Microbiology Center (CGMCC) of China Microbial Culture Collection Management Committee, Address: No. 3, No. 1, Beichen West Road, Chaoyang District, Beijing, Chinese Academy of Sciences Institute of Microbiology, the deposit number is: CGMCC No.13649. The fermentation culture of Streptomyces sp. SCSIO 15077 of the present invention is capable of producing a novel compound tunicamycin E, as shown in formula (I). The invention provides a biological preparation method for the production and preparation of tunicamycin, and has broad application prospects.
Description
The technical field is as follows:
the invention belongs to the technical field of microorganisms, and particularly relates to Streptomyces sp SCSIO 15077 and a neomycin E extracted and separated from the strain.
Background art:
natural products have been an important source for innovative drug development. According to the statistics of Newman D J and Cragg G M, 49 percent of the medicines approved by the United states Food and Drug Administration (FDA) during the period of three decades from 1981-2014 are derived from natural products and derivatives thereof. Wherein, 80% of the anti-tumor drugs and 50% of other drugs are derived from natural products and derivatives thereof. The ocean contains abundant biological resources, the biomass of which accounts for about 87 percent of the total amount of the terrestrial organisms, and the variety of the marine organisms is as much as 20 to more than ten thousand. The marine environment has special environments such as high salt, high pressure, low temperature, low oxygen, low nutrition, low illumination and the like, and actinomycetes living in the marine environment can synthesize secondary metabolites with unique activity and novel structure, so that the actinomycetes can be used as important drug source microorganisms for a long time to be applied to research and development of antibiotics, anti-tumor drugs and other drugs. After the new century, with the deep sea exploration of human beings, the research of the secondary metabolite with the new structure in the marine actinomycetes as the drug lead compound shows a rapid growth trend, and the secondary metabolite is a rapidly rising emerging field.
Tunicamycin belongs to nucleoside antibiotics and consists of four units, namely uracil (uracil), chlamydomonas sugar (tunicamine), N-acetylglucosamine (GlcNAc) and an aliphatic chain. Tunicamycin was originally isolated from streptomyces s, chartreussis, by japanese scholars, but as a mixture. According to statistics, the strains Clavibacter species, S.chartreusis and Corynebacterium rathayi can produce the antibiotics. At present, 37 monomeric compounds of tunicamycin are obtained by co-separation, and named after tunicamycins, streptovirins, mycosporins, MM 19290 and coresyntoxins. Tunicamycin has good inhibitory effect on most gram-positive bacteria and fungi. Wherein the average value of the Minimum Inhibitory Concentration (MIC) of Bacillus thuringiensis (Bacillus thuringiensis) is 1.27 mu g/mL, which is superior to positive controls such as vancomycin and kanamycin. MIC for Candida albicans (Candida albicans) was 2-32. mu.g/mL. Due to the unique pharmacological actions, tunicamycin is expected to be developed into a novel antibacterial and bactericidal medicine.
The invention content is as follows:
one of the objectives of the present invention is to provide a Streptomyces marinus (Streptomyces sp.) SCSIO 15077 capable of producing tunicamycin E, which is deposited in the common microorganism center of the china committee for culture collection of microorganisms (CGMCC) at 23 months 1 in 2017, with the address: the collection number of the microbial research institute of the Chinese academy of sciences, No. 3 Xilu-Beijing province, Chaoyang, and the collection number is: CGMCC No. 13649.
The invention also provides a tunicamycin E which is a novel tunicamycin compound shown in a formula (I):
the invention also aims to provide application of Streptomyces sp SCSIO 15077 in preparation of tunicamycin E.
The fourth purpose of the invention is to provide a preparation method of tunicamycin E, wherein the tunicamycin E is prepared from a fermentation culture of Streptomyces sp SCSIO 15077.
According to the invention, the tunicamycin E is preferably prepared from a fermentation culture of Streptomyces sp SCSIO 15077, and specifically comprises the following steps:
(a) preparing a fermentation culture of Streptomyces marinus (Streptomyces sp.) SCSIO 15077, separating fermentation supernatant and mycelium of the fermentation culture, extracting the fermentation supernatant with butanone, concentrating butanone phase to obtain extract A, soaking and extracting mycelium with acetone, and concentrating acetone leaching liquor to obtain extract B;
(b) and combining the extract A and the extract B, performing silica gel column chromatography by using chloroform-methanol as an eluent in a volume ratio of 100: 0. 95: 5. 9: 1. 8: 2. 5: 5. 0:100, performing gradient elution, and collecting chloroform-methanol with the volume ratio of 5: 5. 0: fractions Fr.5 and Fr.6 eluted at 100, and fractions Fr.5 and Fr.6 were purified to obtain tunicamycin E.
The fermentation culture for preparing the marine Streptomyces sp SCSIO 15077 is prepared by the following method:
inoculating Streptomyces marinus (Streptomyces sp.) SCSIO 15077 into a seed culture medium, fermenting to obtain a seed culture solution, inoculating the seed culture solution into a fermentation culture medium, and fermenting to obtain a fermentation culture, wherein the seed culture medium and the fermentation culture medium are both prepared from the following formula: 4g/L of glucose, 4g/L of yeast extract, 10g/L of malt extract powder, 30g/L of sea salt and the balance of water.
The fifth purpose of the invention is to provide the application of tunicamycin E in preparing antibacterial drugs.
An antibacterial agent characterized by containing an effective amount of the aforementioned tunicamycin E as an active ingredient.
Preferably, the antibacterial drug is a drug against bacillus thuringiensis or candida albicans.
The invention provides a marine Streptomyces sp (Streptomyces sp) SCSIO 15077 capable of producing tunicamycin antibiotics, and a new compound tunicamycin E can be prepared by using the strain, so that a biological preparation method is provided for the production and preparation of tunicamycin, and the strain has a wide application prospect.
The Streptomyces (Streptomyces sp.) SCSIO 15077 is deposited in the common microorganism center of the china committee for culture collection management (CGMCC) in 2017 at 1 month 23, and the address: the collection number of the microbial research institute of the Chinese academy of sciences, No. 3 Xilu-Beijing province, Chaoyang, and the collection number is: CGMCC No. 13649.
Description of the drawings:
FIG. 1 is a morphogram of Streptomyces maritima (Streptomyces sp.) SCSIO 15077 on M-ISP4 medium;
FIG. 2 is a phylogenetic tree of Streptomyces maritima (Streptomyces sp.) SCSIO 15077, where SCSIO S15077 represents Streptomyces maritima (Streptomyces sp.) SCSIO 15077;
FIG. 3 is an HPLC chromatogram of Streptomyces marinensis (Streptomyces sp.) SCSIO 15077 fermentation for production of Tunicamycin E (Tunicamycin E in the figure).
The specific implementation mode is as follows:
the following examples are further illustrative of the present invention and are not intended to be limiting thereof.
Example 1: isolation and identification of Streptomyces maritima (Streptomyces sp.) SCSIO 15077
The marine Streptomyces (Streptomyces sp.) SCSIO 15077 is separated from sediment samples with the water depth of-3536 m in the north of the south sea of China.
The taxonomical characteristics of the strain are as follows:
1. morphological characteristics:
the bacterial colony is dry, the single bacterial colony is generally round, smaller, more compact, not easy to diffuse, the middle is convex, the substrate hypha and the aerial hypha are combined closely and not easy to pick up, and the spores are easy to scrape after the spores are produced at the end stage. White aerial hyphae and yellow matrix hyphae were formed on ISP-4 medium (shown in FIG. 1).
2. Molecular biology separation characteristics:
the genomic DNA of the above isolated strain was extracted, and its 16S rDNA sequence (the nucleotide sequence of which is shown in SEQ ID NO. 1) was PCR-amplified by a conventional method, and sequencing analysis was performed to construct a phylogenetic tree based on the 16S rDNA sequence (shown in FIG. 2), indicating that the sequence similarity of the strain SCSIO S15077 and Streptomyces xinghaiensis S187(CP023202.1)16S rDNA was 99%, indicating that the strain SCSIO S15077 belongs to Streptomyces (Streptomyces xinghaiensis).
In summary, the strain SCSIO S15077 is identified as belonging to a species of Streptomyces, named as Streptomyces sp SCSIO 15077, which was deposited in the china general microbiological culture collection center (CGMCC) on 23/1/2017 at the address: the collection number of the microbial research institute of the Chinese academy of sciences, No. 3 Xilu-Beijing province, Chaoyang, and the collection number is: CGMCC No. 13649.
Example 2: separation and identification of tunicamycin E
1. Preparation of a fermentation culture of marine Streptomyces (Streptomyces sp.) SCSIO 15077:
(1) preparing a seed culture medium and a fermentation culture medium:
a) preparing a seed culture medium: each liter of the seed culture medium contains 4g of glucose, 4g of yeast extract, 10g of malt extract powder, 30g of sea salt and the balance of tap water, and the components are uniformly mixed and the pH value is adjusted to 7.0. 1L of seed culture medium is prepared, then evenly distributed in 20 conical flasks of 250mL, each flask is filled with 50mL of seed culture medium, and sterilized for 30min at 121 ℃ for later use.
b) Preparation of a fermentation medium: each liter of fermentation medium contains 4g of glucose, 4g of yeast extract, 10g of malt extract powder, 30g of sea salt and the balance of tap water, and the components are uniformly mixed and the pH value is adjusted to 7.0. Preparing 1L of fermentation medium, uniformly distributing into 5 1L conical flasks, and sterilizing at 121 deg.C for 30 min.
(2) Culturing seeds:
activated Streptomyces marinus (Streptomyces sp.) SCSIO 15077 (preservation number: CGMCC No.13649) was inoculated into a 250mL conical flask containing 50mL of seed medium, and cultured on a shaker at 28 ℃ and 200rpm for 24 hours to obtain a seed culture solution.
(3) Large-scale fermentation culture:
transferring 50mL of seed culture solution in the conical flask into a 1L conical flask filled with 200mL of fermentation medium, and culturing for 7 days on a shaking table at 28 ℃ and 200r/min to obtain a fermentation culture of Streptomyces marinus (Streptomyces sp.) SCSIO 15077.
2. Isolation of tunicamycin E from Streptomyces sp SCSIO 15077
(1) Extraction of fermentation cultures
Centrifuging a fermentation culture of Streptomyces sp SCSIO 15077 (3800-4000 r/min, 10-15 min) to separate a fermentation supernatant from mycelia; performing isovolumetric extraction on the fermentation supernatant for 3 times by using butanone, and performing rotary evaporation, condensation and concentration on a butanone phase to obtain an extract A; soaking and extracting the mycelium with acetone (2L), performing ultrasonic treatment to obtain acetone extract, and performing rotary evaporation, condensation and concentration on the acetone extract to obtain extract B.
(2) Extraction of tunicamycin E
And (3) analyzing by HPLC, wherein the components of the extract A and the extract B are similar, combining the extract A and the extract B, performing normal-phase silica gel column chromatography, using chloroform-methanol as a mobile phase, and performing separation according to the volume ratio of 100: 0. 95: 5. 9: 1. 8: 2. 5: 5. 0:100, and the fraction eluted with a 100% chloroform gradient is designated as fr.1, the chloroform-methanol volume ratio is 95: the fraction eluted with a gradient of 5 was designated as Fr.2, the chloroform-methanol volume ratio was 9: the fraction eluted with a gradient of 1 is designated as Fr.3, the chloroform-methanol volume ratio is 8: the fraction eluted with a gradient of 2 was designated as Fr.4, the chloroform-methanol volume ratio was 5: the fraction eluted with a gradient of 5 was designated as Fr.5, the chloroform-methanol volume ratio was 0: the fraction eluted at a gradient of 100 was designated Fr.6.
The fractions Fr.1 to 6 were analyzed by HPLC, and it was found that the fractions Fr.5 and Fr.6 contained tunicamycin E, and the combined fractions Fr.5 and Fr.6 were separated and purified by reversed-phase ODS (YMC-Pack ODS-A column, 250X 20mm,5 μm) semi-preparative HPLC (mobile phase CH)3CN/H2Isocratic elution with O50% v/v for 30min at a flow rate of 2.5mL/min (as shown in FIG. 3) gave 10mg of Compound 1 (retention time 15.8min), i.e., tunicamycin E.
(3) Identification of tunicamycin E
Through structural analysis, the identification results of the compound 1 prepared from the fermentation culture of Streptomyces marinus (Streptomyces sp.) SCSIO 15077 according to the present invention are as follows:
compound 1 is white powder, formula C37H60N4O16，HR-ESI-MS m/z 839.3895([M+Na]+)；[α]25 D+43.3(c 0.07，MeOH)；UV(MeOH)λmax(logε)206.00(3.88)，259.40(3.98)nm；IR(film)vmax3308，2924，2853，1665，1551，1466，1377，1260，1092，1023cm-1. In one-dimensional NMR, 3 methyl signals (. delta.) are suggestedC22.8，C-8”；δC22.4，C-11”'；δC13.9, C-14 "'); 10 methylene letter (. delta.)C35.3，C-6'；δC60.5，C-6”；δC31.2，C-4”'；δC27.8，C-5”'；δC29.0-28.6，C-6”'，C-7”'，C-8”'；δC38.4，C-9”'；δC22.0，C-12”'；δC31.2, C-13 "'); 16 methines; 4 olefin carbon signals (. delta.)C102.1，C-5；δC140.3，C-6；δC124.7，C-2”'；δC142.4, C-3') and 4 carbonyl carbon signals (. delta.))C150.8，C-2；δC163.0，C-4；δC169.2，C-7”；δC166.1，C-1”')。1High field in H NMR spectrumOf two fatty chainsH0.79(3H, m, Me-11') and ΔH0.81(3H, m, Me-14 '), correlation of H-14' with C-9 ', C-10' and C-12 'by HMBC H-11', and combination of H-14 'with C-12' and C-131H-1The correlation of H-9 '/H-10 '/H-11 ' and H-10 '/H-12'/H-13'/H-14' in H COSY finally determines the signal deltaH0.87 methyl at C-10 "'. Review of the literature, NMR data of Compound 1 and literature [ Myers A G, Gin D Y, Rogers D H. ChemInform Abstract: Synthetic students of the diagnostic of (+) -diagnostic of viral-viral, and 5' -epi-viral-V [ J].Cheminform,1994,25(46).]The comparison of the reported NMR data of tunicamycin identifies that the compound 1 is a novel tunicamycin antibiotic, namely tunicamycin E, the structure of which is shown in a formula (I), and the data of a carbon spectrum and a hydrogen spectrum are shown in a table 1:
TABLE 1 NMR and Hydrogen spectra data for tunicamycin E
aMeasured in DMSO-d6.
After the crude extract is tested by a filter paper bacteriostatic ring method, the compound 1 is found to have certain bacteriostatic activity on most gram-positive bacteria and candida albicans. Selecting Bacillus thuringiensis BT01(Bacillus thuringiensis), Bacillus thuringiensis W102(Bacillus thuringiensis) and Candida albicans ATCC 96901(Candida albicans) with larger inhibition zone and good activity, and measuring the minimum inhibition concentration by a 96-well plate method by using Candida 98001(Candida albicans). The Minimum Inhibitory Concentration (MIC) of the compound 1 to two strains of Bacillus thuringiensis (Bacillus thuringiensis) is 0.5 and 2.0 mu g/mL, which is superior to the positive control of kanamycin and ampicillin. MICs for two Candida albicans strains (Candida albicans) were 8.0 and 32. mu.g/mL, respectively. The test results are shown in table 2.
TABLE 2 MIC values (μ g/mL) for Compound 1
a Bacillus thuringiensis BT01.b Bacillus thuringiensis W102.c Candida albicans ATCC 96901.d Candida albicans CMCC(F)98001.e These compounds were used as positive controls.
Sequence listing
<110> Nanhai ocean institute of Chinese academy of sciences
<120> marine streptomycete and tunicamycin compound and preparation method thereof
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1407
<212> DNA
<213> Streptomyces SCSIO 15077(Streptomyces sp. SCSIO 15077)
<400> 1
gcttaccatg cagtcgaacg atgaacctct tcggagggga ttagtggcga acgggtgagt 60
aacacgtggg caatctgccc tgcactctgg gacaagccct ggaaacgggg tctaataccg 120
gatacgacca tctcgggcat ccgatggtgg tggaaagctc cggcggtgca ggatgagccc 180
gcggcctatc agcttgttgg tggggtgatg gcctaccaag gcgacgacgg gtagccggcc 240
tgagagggcg accggccaca ctgggactga gacacggccc agactcctac gggaggcagc 300
agtggggaat attgcacaat gggcggaagc ctgatgcagc gacgccgcgt gagggatgac 360
ggccttcggg ttgtaaacct ctttcagcag ggaagaagcg tgagtgacgg tacctgcaga 420
agaagcaccg gctaactacg tgccagcagc cgcggtaata cgtagggtgc gagcgttgtc 480
cggaattatt gggcgtaaag agctcgtagg cggcttgtcg cgtcggatgt gaaagcccgg 540
ggcttaaccc cgggtctgca ttcgatacgg gcaggctaga gttcggtagg ggagatcgga 600
attcctggtg tagcggtgaa atgcgcagat atcaggagga acaccggtgg cgaaggcgga 660
tctctgggcc gatactgacg ctgaggagcg aaagcgtggg gagcgaacag gattagatac 720
cctggtagtc cacgccgtaa acgttgggaa ctaggtgtgg gcgacattcc acgtcgtccg 780
tgccgcagct aacgcattaa gttccccgcc tggggagtac ggccgcaagg ctaaaactca 840
aaggaattga cgggggcccg cacaagcggc ggagcatgtg gcttaattcg acgcaacgcg 900
aagaacctta ccaaggcttg acatacaccg gaaagccgta gagatacggt cccccttgtg 960
gtcggtgtac aggtggtgca tggctgtcgt cagctcgtgt cgtgagatgt tgggttaagt 1020
cccgcaacga gcgcaaccct tgttctgtgt tgccagcatg cctttcgggg tgatggggac 1080
tcacaggaga ctgccggggt caactcggag gaaggtgggg acgacgtcaa gtcatcatgc 1140
cccttatgtc ttgggctgca cacgtgctac aatggccggt acaatgagct gcgataccgt 1200
gaggtggagc gaatctcaaa aagccggtct cagttcggat tggggtctgc aactcgaccc 1260
catgaagtcg gagtcgctag taatcgcaga tcagcattgc tgcggtgaat acgttcccgg 1320
gccttgtaca caccgcccgt cacgtcacga aagtcggtaa cacccgaagc cggtggccca 1380
acccgtgagg gagggaatcg tcgaagt 1407
Claims (10)
1. Streptomyces sp.SCSIO 15077, with the deposit number: CGMCC No. 13649.
2. Tunicamycin E, the chemical structural formula of which is shown in formula (I):
3. use of Streptomyces sp.SCSIO 15077 of Streptomyces marinus according to claim 1 for the preparation of tunicamycin E according to claim 2.
4. A process for the preparation of tunicamycin E according to claim 2, characterised in that tunicamycin E is prepared from the fermentation culture of Streptomyces sp.SCSIO 15077 according to claim 1.
5. The preparation method of tunicamycin E according to claim 4, characterized in that it comprises the following steps:
(a) preparing a fermentation culture of Streptomyces sp.SCSIO 15077, separating fermentation supernatant and mycelium of the fermentation culture, extracting the fermentation supernatant with butanone, concentrating butanone to obtain an extract A, soaking and extracting the mycelium with acetone, and concentrating acetone leaching liquor to obtain an extract B;
(b) and combining the extract A and the extract B, performing silica gel column chromatography by using chloroform-methanol as an eluent, and performing column chromatography on the mixture in a volume ratio of 100:0 to 95: 5. 9: 1. 8: 2. 5: 5. performing gradient elution at a ratio of 0:100, collecting chloroform-methanol at a volume ratio of 5: 5. and (3) purifying the eluted fractions Fr.5 and Fr.6 and the fractions Fr.5 and/or Fr.6 at a ratio of 0:100 to obtain tunicamycin E.
6. The method according to claim 5, wherein the fermentation culture for producing Streptomyces sp.SCSIO 15077 is prepared by:
inoculating Streptomyces sp.SCSIO 15077 into a seed culture medium, fermenting to obtain a seed culture solution, inoculating the seed culture solution into a fermentation culture medium, and fermenting to obtain a fermentation culture, wherein the seed culture medium and the fermentation culture medium are both prepared from the following components: 4g/L of glucose, 4g/L of yeast extract, 10g/L of malt extract powder, 30g/L of sea salt and the balance of water.
7. Use of tunicamycin E according to claim 2 for the preparation of an antibacterial medicament.
8. The use of claim 7, wherein the antibacterial agent is against Bacillus thuringiensis or Candida albicans.
9. An antibacterial agent characterized by containing an effective amount of tunicamycin E of claim 2 as an active ingredient.
10. The antibacterial agent of claim 9, wherein said antibacterial agent is against bacillus thuringiensis or candida albicans.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810481038.3A CN108660093B (en) | 2018-05-18 | 2018-05-18 | A kind of marine streptomyces, tunicamycin compounds and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810481038.3A CN108660093B (en) | 2018-05-18 | 2018-05-18 | A kind of marine streptomyces, tunicamycin compounds and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108660093A CN108660093A (en) | 2018-10-16 |
| CN108660093B true CN108660093B (en) | 2021-07-20 |
Family
ID=63776861
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810481038.3A Active CN108660093B (en) | 2018-05-18 | 2018-05-18 | A kind of marine streptomyces, tunicamycin compounds and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108660093B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114539355A (en) * | 2020-11-26 | 2022-05-27 | 南京碳硅人工智能生物医药技术研究院有限公司 | Non-ribosome peptide compound bosamycinI and preparation method thereof |
| CN114317338A (en) * | 2021-12-21 | 2022-04-12 | 北京工商大学 | Streptomyces and application thereof in preparation of antibacterial drugs |
| CN115806907A (en) * | 2022-10-20 | 2023-03-17 | 中国科学院沈阳应用生态研究所 | Preparation and application of a deep-sea streptomyces and its antifeedant and antifungal active substances |
| CN116925967B (en) * | 2023-07-18 | 2024-12-24 | 青岛大学 | Marine streptomycete and application of oligomycin products thereof in resisting agricultural pathogenic bacteria |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102168034A (en) * | 2010-11-29 | 2011-08-31 | 中国科学院南海海洋研究所 | Marine streptomyces and method for preparing tirandamycin A and B by utilizing strain |
-
2018
- 2018-05-18 CN CN201810481038.3A patent/CN108660093B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102168034A (en) * | 2010-11-29 | 2011-08-31 | 中国科学院南海海洋研究所 | Marine streptomyces and method for preparing tirandamycin A and B by utilizing strain |
Non-Patent Citations (2)
| Title |
|---|
| Isolation,stereochemical study,and cytotoxic activity of isobenzofuran derivatives from a marine Streptomyces sp.;Shu-Min Zhang et al.;《Chirality》;20141014;第27卷(第1期);第82-87页 * |
| 生物与化学方法相结合提高海洋生境放线菌YB-24菌株星形孢菌素产量;盖翠娟等;《中国抗生素杂志》;20150531;第40卷(第5期);第325-329页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108660093A (en) | 2018-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108660093B (en) | A kind of marine streptomyces, tunicamycin compounds and preparation method thereof | |
| JPH0734740B2 (en) | Actinomycetes capable of producing antibacterial CL-1577 | |
| CN101245362A (en) | Method for producing polypeptide antibiotic amycin by fermentation method | |
| CA1291054C (en) | Antitumor antibiotics (ll-e33288 complex) | |
| CN111057669A (en) | Strain for improving yield of tetramycin Z and method for preparing tetramycin Z by using same | |
| CN107365811B (en) | Fermentation technology for producing rapamycin using actinomycetes | |
| CN104087523B (en) | A kind of marine streptomyces and utilize it to prepare the application of the method for Enterocin and this bacterium | |
| CN109810919B (en) | A class of Ansa all-carbocyclic polyketone antibiotics and its application in the preparation of antibacterial drugs or antitumor drugs | |
| CN107686817A (en) | One plant of fetid marsh fleabane endogenetic fungus CYSK 4 and its Ascomylactam class compounds of production application | |
| CN109280034B (en) | Benzoxazepine compound with antibacterial activity and preparation method and application thereof | |
| CN115109023B (en) | Macrolide compound FWYZ52-A, its fermentation strain, fermentation method and application | |
| CN116179359B (en) | Marine penicillium pi and its culture method and application | |
| CN102965300B (en) | Micromonospora strain, its preparation method and application | |
| CN110092758B (en) | A novel alkaloid compound and verrucospora strain for preparing the compound by fermentation | |
| CN113980860B (en) | Nonomuria with high yield of prastatin and 2 '-amino-2' -deoxyadenosine and application thereof | |
| CN113337432B (en) | Methylophilus for producing pyrroloquinoline quinone and application thereof | |
| CN114907367A (en) | Macrolide compound FW-Z, its fermentation strain, fermentation method and application | |
| CN1923825A (en) | Novel antibiotic Chemomycin A and preparation method thereof | |
| CN110343639B (en) | Streptomyces producing 15(S) -O-ethyl rapamycin | |
| CN108485991B (en) | A marine saccharopolyspora and its application in the preparation of erythromycin derivatives | |
| CN117050921B (en) | A new type of marine Streptomyces that produces anthracin and β-rubimycin and its application | |
| CN116874417B (en) | Pyridine alkaloid and application thereof in preparation of antitumor drugs | |
| CN109628520B (en) | Fermentation medium for increasing yield of non-viable bacteria and application thereof | |
| CN116179400B (en) | A myxobacteria producing rearranged steroid compounds and their applications | |
| JPH0374388A (en) | Novel microbiologically transformed l-683, 590 products |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: No.1119 Haibin Road, Nansha District, Guangzhou City, Guangdong Province Applicant after: SOUTH CHINA SEA INSTITUTE OF OCEANOLOGY, CHINESE ACADEMY OF SCIENCES Address before: 510301 No. 164 West Xingang Road, Guangzhou, Guangdong, Haizhuqu District Applicant before: SOUTH CHINA SEA INSTITUTE OF OCEANOLOGY, CHINESE ACADEMY OF SCIENCES |
|
| CB02 | Change of applicant information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |