JPS63152992A - Antibiotic substance tan-876 and production thereof - Google Patents

Abstract

PURPOSE:To obtain the novel antibiotic substance TAN-876 useful as a medicine, agricultural chemical and animal drug effective against bacteria and fungi including resistant strains, by culturing a microbial strain belonging to Streptomyces genus and separating the objective substance from cultured product. CONSTITUTION:A microbial strain belonging to Streptomyces genus and capable of producing antibiotic substance TAN-876 of formula I (R<1> is hydroxyl group; R<2> is H; R<1> and R<2> may together form an ether bond), e.g. Streptomyces C-70899 (FERM P-8807) is cultured in a medium, preferably a liquid medium containing a carbon source such as starch, glucose, etc., a nitrogen source such as soybean flour, peptone, etc., and inorganic salts, etc., e.g. at 6-8pH and 24-36 deg.C for 48-120hr. The objective antibiotic substance TAN-876 is present in the microbial cell and filtrate. It is extracted with an organic solvent such as chloroform, ethyl acetate, etc., concentrated and subjected to purification and fractionation by chromatography, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel antibiotic TAN-876 (rTAN-876J) useful as a therapeutic agent for bacterial and fungal infections.
It is sometimes abbreviated as. ) and its manufacturing method.

Prior Art An antibiotic relatively similar to the present antibiotic is cervicarcin [Journal of the American Chemical Society].
fAmerican Chemical 5oci
ety), 86Q, p. 4507 (1964)] or Nanaomycin [Journal of Antibiotics].
f Antibiotics), volume 28, page 868 (
(1975)], but these are halogen-free compounds and are different from the present antibiotic.

Problems to be Solved by the Invention Diseases caused by bacteria have been largely overcome by the development of therapeutic methods by administering antibiotics.

However, the increase in diseases caused by long-term or large-dose administration of conventional antibiotics and the appearance of resistant bacteria, as well as the increase in fungal diseases due to weakened immunity, are major problems in the current field of infectious disease treatment. It has become. To overcome this problem, the field is constantly looking for antibiotics that have novel skeletons and exhibit excellent biological activity, or intermediate raw materials for synthesizing them.

Means for Solving the Problems In view of the current situation, the present inventors conducted repeated research on therapeutic agents for bacterial infections from a new perspective, and found that among the large number of microorganisms isolated from soil, certain The microorganism produces a new antibiotic, the microorganism belongs to the genus Streptomyces, and the microorganism is cultured in an appropriate medium.
Antibiotics that exhibit antibacterial activity against bacteria such as Durham-positive bacteria, acid-fast bacteria, including resistant bacteria, and fungi such as medical fungi, yeast, and plant pathogenic bacteria are accumulated in the culture medium. We isolated this antibiotic and confirmed that it was a new antibiotic based on its physicochemical and biological properties, and decided to name it antibiotic TAN-876. Antibiotic TAN-876 consists of two components, which are referred to as TAN-876A and B, respectively. The present inventors completed the present invention as a result of further research based on these findings.

That is, the present invention provides for culturing (1) antibiotic TAN-876 or a salt thereof, and (2) antibiotic TAN-876-producing bacteria belonging to the genus Streptomyces in a medium, and producing antibiotic TAN-876 in the culture. The present invention relates to a method for producing antibiotic TAN-876, which is characterized by accumulating and collecting the precipitate.

The bacterium that produces the antibiotic TAN-876 used in the method of the present invention is Streptomyces (S Lrepto
Any microorganism may be used as long as it belongs to the genus S+yces and has the ability to produce the antibiotic TAN-876. An example is C-7089 isolated from soil.
The mycological properties of this strain are as follows. In addition, unless otherwise specified, the properties on the various media are those obtained by culturing at 28°C for 14 days and observing according to conventional methods.The color tones are based on the Color Harmony Manual (Co
lorHarmony Manual) 4th Edition [Container - Corporation Fist of America (Container
tainerCorporation or Am
Erica), published in 1958.

! Formation of aerial hyphae and spores is abundantly observed on media such as yeast/malt agar, starch inorganic salt agar, and glycerol/asparagine agar. The branches of the aerial hyphae are simple branches, no axle branches are observed, and a spiral chain of spores is observed at the tip. No special structures such as sclerotia or sporangia are observed. When observed using an electron microscope, the surface of the spores is smooth, and the shape of the spores is spherical, oval, or short cylindrical, and their sizes are 0.8 to 1.2xo, 8 to 1°0.
Microns, usually 20 or more in a chain.

2. Sex on various classification media! (Culture at 28°C for 14 days) 1) Growth on sucrose/nitrate agar medium: Moderate, light yellow (11/2ea) to dusty yellow (z 1/2gc) Aerial mycelium: poor to moderate, white underside color : Butter Yellow (l l/2ga) ~ Bamboo (2gc) Soluble pigment: None 2) Yeast/malt agar growth: Moderate to good, Clove brown (apl)
) Aerial mycelium: Abundant, silver/gray (3fe) Back color:
Clove Brown (3 pl) Soluble pigment: None 3) Oat Meal Agar Medium Growth: Medium, Light Ipoly- (2 ca) Aerial Mycelium:
Medium, adobe brown (31g) Underside color Nirite Spice Brown (41g) Soluble pigment: brown to tan 4) Starch inorganic salt agar growth: Medium Mustard brown (2ni) Aerial mycelium:
Rich, natural (2dC) to silver gray (3"
e) Back side color: Mustard brown (2ni) ~ Covert brown (2nl) Soluble pigment: None 5) Glycerol-asparagine agar growth: Medium, light mustard tan (2ie) Aerial mycelium: Abundant, natural ( 2dc) ~ Natural (3
dc) ~ Silver Gray (3fe) Back color: Bamboo (2gc) ~ Mustard Tan (2
1g) Soluble dye: None 6) Glucose-asparagine agar medium Growth: Moderate;
Colorless aerial mycelium: medium, solver gray (3re) ~ Ashes (5rc) Underside color: colorless ~ light mustard tan (2ie) Soluble pigment: none 7) Peptone yeast iron agar medium growth: medium, Byjie Brown (3), which causes wrinkles
ig) Color of underside without double epiphyte aerial mycelium: Vizier brown (3ig) Soluble pigment:
Brown to clove brown (3ni) 8) Dirosine agar medium growth: Moderate, brown to dark brown Aerial hyphae: Poor, white Underside color: brown to dark brown Soluble pigment: Light yellowish brown 9) Calcium maleide agar medium growth : Poor, colorless, no epiphyte mycelia Underside color: Colorless to cream (l I/2ca) Soluble pigment: None 3, Physiological properties 1) Growth temperature range: 12-40℃ Optimum temperature range: 22- 37℃ 2) Liquefaction of gelatin: Negative 3) Hydrolysis of starch: Positive 4) Peptonization of milk Negative 5) Coagulation of milk: Negative 6) Reduction of nitrate: Positive 7) Formation of melanin-like pigment: Positive 8) Carbon Source availability D-Sorbitol - Neuclose - l-Inositol + Lactose + D-Mannitol + Raffinose + D-Kinlose +
Trehalose + L-arabinose + Mannose + D-galactose + Soluble starch
Ten-glucose + glycerol + D-fructose + melibiose + rhamnose
+ Maltose + Adonitol +
Aesculin - Erythritol - Salicin + Dulcitol - Inulin
- Cellulose - Ribose + Sorbose - No additives - Basal medium: Bridham and Gottlieb agar 4, analysis of diaminopimelic acid in whole bacterial cell hydrolyzate [Toru Hase et al., Journal of General Applied Microbiology (Journal or General
Applied Microbiology), λy
, 319 (1983)] LL-2,6-tzaminobimelic acid was observed.

To summarize the above mycological properties, C-70899 strain is
The tip of the aerial hyphae has a spiral shape, and the spore surface is rough. The color tone of growth is pale yellow, yellowish brown or brown, and the aerial mycelium is grayish. In addition, melanin-like soluble pigment is produced. Furthermore, since LL-diaminopimelic acid was detected in the bacterial cells, this bacteria belongs to cell wall type 1. Based on the above properties, T'he Actinomycetes, written by Nis ny Waxman,
es) Volume 2, The Williams & Wilkins Company, 1961, and R. E. Bouffanin and N. E. Gibbons, eds., Vernose, Manual of Determinative Pacteriology (Bergey' s Manual
ofDeLearn+1native BacLeri
Bacterial species were searched according to the 8th edition (1974). As a result, Streptomyces resistomicus (Streptomyces resistomyces) was found to be a bacterial species relatively related to the C-70899 strain.
cificus) and Streptomyces neyagawaensis (S.
ensis). In order to conduct a more detailed study on these two bacterial species, we investigated Streptomyces resistomicus IFO12814 and Streptomyces neyagawaensis IFO13477, and found that these two bacterial species differ from strain C-70899 in the following points. Admitted.

Streptomyces resistomicus: yeast
Although open spirals of aerial hyphae are observed on malt agar medium, they generally exhibit an incomplete spiral or tablet-like morphology. In addition, its color tone is light pink (fresh pink, 4 c
a) to light yellowish brown (faun, 4ig). Use sucrose.

Streptomyces neyagawaensis: On yeast malt agar medium, aerial mycelial settlement is generally poor and its color is sandy (3 cb). The morphology of the spores is oblong. Use sucrose.

As mentioned above, no known bacterial species closely related to the C-70899 strain has been recognized at this time.

Therefore, strain C-70899 was recognized as a new bacterial species and named Streptomyces nis p. C-70899.

The C-70899 strain was deposited with the Fermentation Research Institute (IFO) on May 29, 1985 under the accession number IFO14509, and this microorganism was deposited with the Institute of Microbial Technology, Agency of Industrial Science and Technology, Ministry of International Trade and Industry on June 13, 1986. (Fllll) under accession number FERM P-8807.

The bacteria that produces the antibiotic TAN-876, which belongs to the genus Streptomyces, is susceptible to changes in its properties, such as exposure to ultraviolet rays,
They are easily mutated by artificial mutagenesis methods using radiation, artificial mutagens, etc., and even such mutant strains that have the ability to produce the antibiotic TAN-876 can be used in the method of the present invention. It can be used.

In the method of the present invention, the medium in which the antibiotic TAN-876-producing bacteria is cultured may be either liquid or solid, but a liquid medium is more conveniently used, and surface culture or shaking culture may also be used. , deep culture methods are more advantageously used. Antibiotic TAN=876 producing bacteria can assimilate carbon into the medium.

Sources such as starch, glucose, dextrin, glycerin, euclose, n-paraffin and alcohols (e.g. methanol); nitrogen sources such as organic nitrogen sources such as corn stew liquor, soybean flour;
Inorganic nitrogen sources such as cottonseed flour, peptone, meat extract, etc. may be used such as ammonium chloride, ammonium sulfate, ammonium nitrate and urea. In addition, as necessary, inorganic salts such as salts containing sodium, potassium, magnesium or phosphorus, heavy metal salts such as iron, manganese, zinc, cobalt, copper and nickel salts, antifoaming agents such as soybean oil, lard oil, chicken porridge, etc. , silicone oil, Actocol (manufactured by Takeda Pharmaceutical Company Limited), etc. may be added as appropriate. In liquid culture, the pH of the medium is preferably around neutral, particularly around pH 6 to 8. Culture temperature is approximately 24℃ ~
The incubation time at 30°C is approximately 48~! 20 hours is preferred.

The titer of the antibiotic TAN-876 produced in the culture solution over the course of the culture is tested according to the conventional method of agar dilution method or paper disc method using Micrococcus flavus IFO3242 as the test bacteria. Usually about 3
The production of antibiotic TAN-876 reaches its maximum after ~4 days of culture.

In order to collect the target antibiotic TAN-876 from the culture, separation means that are normally used to collect metabolites produced by microorganisms from the culture of the microorganisms are appropriately utilized. For example, 'l' AN-876 exhibits acidic and fat-soluble properties and is contained in bacterial cells and filtrate, so solvents that do not mix with water such as chloroform, ethyl acetate, methyl isobutyl ketone, or butanol are added to the culture solution. etc. to extract TAN-876. After washing the extract with water, the organic solvent layer is concentrated.

The concentrate containing TAN-876A and B is further purified and fractionated by adsorption, distribution, or chromatography utilizing the properties of molecular sieves. That is, a method is advantageously used in which the concentrate is brought into contact with a suitable carrier to adsorb the active ingredient, and then the active ingredient is desorbed using a suitable solvent and then separated and collected. Silica gel as a carrier,
Crystalline cellulose, adsorbent resins such as Diaion HP
-20 (manufactured by Mitsubishi Chemical Industries, Ltd.), Amberlight XAD-II (Rohm & Haas L, USA),
Sephadex L) I-20 (manufactured by Farman Fine Chemicals, Sweden) and the like are used. The elution solvent varies depending on the type of carrier, but for example, n-hexane, toluene, chloroform, dichloromethane, ethyl acetate, acetone, alcohols, pyridine, acetic acid, water, or a mixed solvent thereof may be used in an appropriate combination. The eluate containing TAN-876 was concentrated to dryness,
It is crystallized from a suitable solvent such as hexane, diethyl ether, toluene, ethyl acetate, or chloroform, or is powdered by adding petroleum ether or hexane to the concentrated dry product.

If A and B are still not separated by the above chromatography, preparative reverse phase high performance liquid chromatography (■■PLC) may be advantageously used to isolate them. Examples of carriers that can be used include TSK gel (manufactured by Toyodai JJ! Co., Ltd., Japan), YMC gel (manufactured by Yamamura Kagaku Kenkyushin Co., Ltd., Japan), and mobile phases such as acetonitrile or methanol and a buffer solution. A mixture of these should be used.

Note that TAN-876A and B react with cations in alkaline solutions, such as sodium carbonate and sodium ions and potassium ions in potassium carbonate solutions, to form salts. Purification of these salts is carried out in a conventional manner by adsorption chromatography, for example chromatography using Diaion IP-20 as a carrier.

The physicochemical properties of antibiotics TAN-876A and B obtained in Example 1 described below are as follows.

TAN-876A (1) Appearance: pale yellow solid (2) Melting point, >300°C (decomposed) (3) Molecular weight measurement value + (by El-MS method) 331 (
M'') (4) Elemental analysis value (%); Actual value: C: 47.48, If: 2.83, N: 4.4
9, C &: 32.57 Calculated value・C: 46.95, H: 2.42, N・4.21
゜CI2: 31.98, O: 14.43 (5) Molecular formula: C13H8NCC303 (6) Ultraviolet absorption (UV) spectrum (see attached Figure 1) In methanol (indicated by the solid line in Figure 1) λmax 2
42 ± 3 nm (E'% - 980 ± 100) c2 298 ± 3 nm (E'% = 308 ± 50) lCj! 360±3 nm (E1%-318±50) cx Methanol: INt (in CQ(9:I) (indicated by the broken line in Figure 1) λmax 247±3 nm (E1%-1+34 soil 100
) IC shoulder 357 ± 3 nm (E'% - 332 ± 50) cx Methanol: IN Na0II (9:l) (1st
(Indicated by a dashed line in the figure) λmax 242 ± 3 nm (E'% = 830ffilO
O) lc scrap 266±3 nm (E'%=648±50) lct! 300±3nm (E'%-540±50)cx 370±3nm (E''=356±50)cz (7) Optical external absorption (IR) spectrum (see attached Figure 2)・The following main components in KBr Indicates absorption.

3.130.3210.3150.29g0.2950
．． 1615.1590°+570.1530.1440
．． 14+0.1350.1310. +270°125
0, 1230.1170.1080.1060.102
0.980.900°850, 800.780.770
．． 750.710.645.620 (cm-') (8)
'H-Nuclear magnetic resonance (NMR) spectrum = 400M
Hz, dimethyl sulfoxide-d, the following signals were observed.

1.17 (3H, t), 2.62 (2H, Q), 7.6
7 (11 (, s), I 3.55 (I H, s) (pp
m) (s: singled, t: tri
plet, q: indicates quartet) (9) IIPLC + carrier, YMC-PAK A-312
, Mobile phase: 65% acetonitrile 10.01M phosphate buffer (pH 6,3), flow rate: 2xg/win.

Detection method: UV (220 nm) Rt=2.75 (IIlin,) (10) Color reaction positive: Potassium permanganate negative: Burton, magnesium acetate, Dragendorff, ninhydrin, Greig-Lieback reaction (11) Substance classification Lipid-soluble acidic substance 'rAN 876I3 (1) Appearance: Slight yellow solid (2) Molecular weight measurement: (by EIMS method) 333 (M
(4) Elemental analysis value (%): Actual value: C: 46.76, II: 2.99, N: 4.3
3, CQ: 30.83 Calculated value: C: 46.66, H: 3. Ot, N: 4. l
9, CQ: 31.79, O: 14.35 (5) Molecular formula: C++H+oNC(!*0+(6)
UV spectrum: (see attached Figure 3) in methanol (indicated by solid line in Figure 3) λwax 308 ± 3 nm (
E'%-417±50) cx Methanol: IN 11 (J! (9:l) (3rd
(Indicated by a broken line in the figure) λwax 314 ± 3 nm (E'% = 591 ± 50) 1
cm Methanol: IN Na0) [(9:1) (3rd
In the figure, indicated by a dashed line) λmax 321±3 nm (E1%=721±50)c
x (7) In spectrum (see attached Figure 4): KB
r Shows the following main absorptions.

3500, 31F10.29B0.2700.2650
．． 1610.1590°+470.1420.14G0
．． 1330.130G, 1290.126G.

1220, 1200.1155.1080.1050.
1020.980.930°875, 850.790.
770.750.730.690.660゜620゜5
60 (cm-') (8) 'H-NMR spectrum: 400 MHz
, the following signals were observed in dimethyl sulfoxide-d8.

1.10 (311, t), 6.48 (I II, s)
, 7.13 (ILl, s), 8.79 (11-I, s)
, 9.18(lH,s), 13.2(lH,5Xpp
I11) (9) HPLC: Same conditions as component A Rt = 5, l (ffiin, ) (10) Color reaction positive Potassium dipermanganate, Burton, magnesium acetate (yellow) Reaction negative: Dragendorff, ninhydrin , Greig
Liebak reaction (11) Substance classification Lipid-soluble acidic substance The chemical structures of antibiotics TAN-876A and TAN-876B are shown by the following formula.

TAN-876A TAN-876B Tables 1, 2 and 3 show the antibacterial activity of antibiotics TAN-876A and TAN-876B against three types of microorganisms.

Furthermore, acute, 1i using TAN-876A mice
The characteristics are shown in Table 1.

As is clear from the physicochemical and biological properties shown in Table 4 and above, 'l' AN-876A and B are new antibiotics, exhibit strong antibacterial and antifungal effects, and are effective against mammals, etc. It is a useful substance as a medicine, veterinary medicine, and agricultural chemical because it is not toxic to humans.

When using this antibiotic, for example, TAN-87
To use TAN-876 or a salt thereof as a bactericidal agent for bacterial infections, TAN-876- or a salt thereof is mixed with a pharmacologically acceptable carrier, excipient, diluent, etc.
N-876 or its salt is about 0.0% as TAN-876.
A solution or t dissolved in alcohol or water etc. at a concentration of OI ~ 2 w/v%, preferably about 0.1=1 w/v%.
Approximately 0.0 g of TAN-876 per g. OF+-50mg
, preferably as an ointment containing about 0.5 to 20 mg, on the hands of mammalian animals (e.g., humans, cows, horses, dogs, etc.);
By applying it to the feet, face, etc., it can be used to sterilize and disinfect these areas.

The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto.

Note that percentages (%) in the culture medium represent weight/volume percentages unless otherwise specified.

Example 1 Yeast extract/malt extract Streptomyces nis p. C-70899 (IFO-14) cultured on slanted agar medium
509, FERM P-8807) in a 200 yg Erlenmeyer flask with 2% glucose, 3% soluble starch, 1% raw soybean powder, 1% corn stew liquor, and 0 peptone.
40j112 seed medium (pH 7,0) containing 5% NaCQ, 03% NaCQ, 5% CaCO, and incubated at 28°C.
, and cultured on a rotary shaker for 48 hours to obtain a preculture solution. 5IQ of the obtained preculture solution was transferred to a 200Off (5002Q seed medium in a Yosaka Lof flask and cultured on a reciprocating shaker at 28°C for 48 hours to obtain a seed culture solution.This seed culture solution 500TIQ Transplanted into a 30Q seed medium (l:, same composition as the heel medium) in a 50Q stainless steel tank,
Ventilation 30ρ/min, stirring 280 rpm, internal pressure 1kg/c
The cells were cultured under tx' conditions. 5Q of the obtained culture solution was 20
Glucose 05% in 0Q capacity stainless steel tank
, dextrin 5%, defatted soybean flour 3.5%, CoCQ=
+20Q containing 0.0002%, CaCO30.7%
Transplanted to the main medium (pH 7,0) and kept at 28℃, aeration +20
The cells were cultured for 96 hours under the conditions of Q/min, stirring at 180 revolutions/min, and internal pressure of 1 to 9/cm'.

The thus obtained culture solution (100 f2) was diluted with dilute sulfuric acid.
The mixture was adjusted to H4, ethyl acetate (+00Q) was added, and the mixture was stirred for 30 minutes. The mixture of culture solution and organic solvent was filtered using a filter aid. The aqueous layer of the filtrate (170 g) was separated and removed, and the extracted*m solvent layer (85&) was washed with water. The ethyl acetate layer (77) was concentrated under reduced pressure (100 g), and the column was washed once with n-hexane. The antibacterial active fraction was eluted with chloroform (1f2). The eluted fraction was concentrated,
Subjected again to silica gel chromatography (509),
Elution was performed with chloroform, and both fractions containing TAN-876A and TAN-876B were obtained. Both concentrated solutions were further subjected to silica gel chromatography (50 g) and fractionated by elution with toluene and a mixture of toluene and chloroform. The fractions were subjected to analytical 11 PLC and the contents of TAN-876A and B were examined. When both fractions mainly containing TAN-876A were collected and concentrated, a slightly yellow crystal of TAN-876A (120R9) was precipitated. Mainly 'rAN-87
Both fractions containing 6B were collected and concentrated, and n-hexane was added to the concentrated residue to obtain a powder (150 mg). This powder was dissolved in methanol and subjected to preparative 1-I PLC [carrier: YMC-PAK 0DS-S10, mobile phase: 55
% acetonitrile 10.01M phosphate buffer (pt■6
, 3)]. The component content in each fraction was examined using analytical HPLC, and TAN-876B was used to analyze the aqueous layer at pl+3, 5
1. After adjusting the q and extracting with ethyl acetate, washing the extract with water and concentrating, a crystalline powder of TAN-87613 (85 ay
)was gotten.

Example 2 '1゛ΔN876A (90% purity, 150 mg) was dissolved in a 2% sodium carbonate solution (300 m□, and a trace amount of insoluble matter was removed by filtration. The filtrate was mixed with Amberlite XΔI)-1
1 (50 m), and after washing the column with water (400 m), 30% methanol-water (50 m) was applied.
The antibiotic was eluted and fractionated using 50% methanol-water (500 mg) and 50% methanol-water (500 m). The effective fraction (750 m&) was collected, concentrated, and lyophilized to yield a yellow powder (125 mg).

When this powder was dissolved in methanol and left to stand, crystals were precipitated, collected by filtration, and dried to obtain the sodium salt of TAN-876A (95+++ g) as slightly yellow crystals.

Child cord analysis value (%): C+J17NC1s03・Na(
1,5+r2o) Actual value: C: 40. I'l, H: 2.78, N: 3.8
8, C (!: 26.50, Na: 6.8 - * Calculated value: C: 4.0.92, H + 2.64, N: 3.6
7, (J!: 27.87, O: 18.87, Na: 6.
02 (*: Calculated assuming that it contains 1.5 mol of water) rn spectrum - Main absorption in KBr 3450, 3210.29g 0.2940.1610.
1590.1570°1530, 1440.14+0.
1330.13IQ, 1270. +250°122
0, 11? 0.1090.1060.1015.970
．． 900.850°800, 780.770.710.
640 (am-') Melting point: >300°C (decomposition) Effects of the invention TAN 876A and B of the present invention are novel antibiotics produced by Streptomyces, and are effective against bacteria and fungi including resistant bacteria. Since it is effective, it is useful as a medicine, agricultural chemical, or veterinary medicine.

[Brief explanation of the drawing]

Figure 1 shows the ultraviolet absorption spectrum of the novel antibiotic TAN-876 of the present invention, and Figure 2 shows its infrared absorption spectrum.
Figure 3 shows the ultraviolet absorption spectrum of 'l'AN-876I3, and Figure 1 shows its optical external absorption spectrum.

Claims (2)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^1 represents a hydroxyl group and R^2 represents hydrogen,
R^1 and R^2 represent an ether bond. ] Antibiotic TAN-876 or a salt thereof. (2) Antibiotic TAN-8 belonging to the genus Streptomyces
76-producing bacteria were cultured in a medium, and the antibiotic TAN was added to the culture.
A method for producing the antibiotic TAN-876, which comprises producing and accumulating TAN-876 and collecting it.