JPH06199882A - New antifungal antibiotic substance w7176b and w7176c and production thereof - Google Patents

Abstract

PURPOSE:To obtain antibiotic substances W7176B and W7176C expected of their use as an antifungal agent and a method for producing them. CONSTITUTION:These antibiotic substances are obtained by culturing a microorganism belonging to genus Streptomyces, e.g. Streptomyces.versipellis Mer-W7176 strain (FERM P-13273) in a nutrient culture medium, separating microbial cells from the resultant culture solution, extracting the separated microbial cells with a solvent and further isolating and purifying the resultant extract by using an adsorbent resin, centrifugal partition chromatography, a gel filtration agent, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel antifungal antibiotic and a method for producing the same.

[0002]

Conventionally, as antifungal substances, polyene substances such as amphotericin B, nystatin and tricomycin, imidazole substances such as miconazole and ketoconazole, and triazole substances such as fluconazole have been known. Fungal substances have selective toxicity,
There is a problem in medicinal efficacy and the like, and it cannot be said to be sufficient as a therapeutic agent for fungal infections.

[0003]

The present invention provides a novel antifungal antibiotic having a strong antibacterial activity against fungi having pathogenicity.

[0004]

[Means for Solving the Problems] The present inventors isolated strains from various soils for the purpose of searching for novel antifungal substances, and conducted repeated research on the metabolites produced by the strains. Strains belonging to the genus Streptomyces (Streptomyces), a substance showing antibacterial activity against Candida albicans (Aspergillus fumigatus), which is the causative bacterium of fungal infections in the culture medium, etc. I found that they are producing. When the active substance was separated and purified from the culture solution and its physicochemical properties were examined, the active substance was found to be dunaimycins (The Journal of Antibiotics 44, 1318-1330 (1991)).
The present invention has been completed by finding that it is a novel substance which has not been described in the conventional literature presumed to have a structure similar to that and has excellent antifungal activity.

That is, the present invention provides an antifungal substance W7176B having the following physicochemical properties. (1) Appearance: White powder (2) High-resolution FAB mass spectrum m / z; 912.6055 (M + H) ⁺ (3) FAB mass spectrum (matrix; m-nitrobenzyl alcohol) m / z; 912 (M + H) ) ⁺ (4) Molecular formula: C ₄₉ H ₈₅ O ₁₄ N

(5) Optical rotation [α] ²⁷ _D -15 ° (C = 0.5, methanol solution) (6) UV absorption spectrum The results of measurement with a methanol solution are as shown in FIG. (7) IR absorption spectrum The result measured in the KBr tablet is as shown in FIG. (8) ¹ H-NMR spectrum The spectrum measured with deuterated chloroform at 400 MHz is shown in FIG.
As shown in. (9) ¹³ C-NMR spectrum The spectrum measured at 100 MHz in deuterated chloroform is shown in FIG.
As shown in.

(10) Solubility Soluble in methanol, acetone, ethyl acetate and chloroform. Insoluble in n-hexane. (11) Color reaction Positive: Anisaldehyde sulfuric acid reaction, phosphomolybdic acid reaction, iodo reaction Negative: Ninhydrin reaction (12) Rf value of thin layer chromatography 0.28 on silica gel plate F-254 (Merck) (developing solvent (Toluene: Acetone: Ammonia = 2: 1: 0.001) (13) Distinction between basic, neutral and acidic Basic

The present invention further provides an antifungal substance W7176C having the following physicochemical properties. (1) Appearance: White powder (2) FAB mass spectrum (matrix; m-nitrobenzyl alcohol) m / z; 894 (M + H) ⁺ (3) Molecular formula: C ₄₉ H ₈₃ O ₁₃ N (4) UV absorption Spectrum The result of measurement with the methanol solution is as shown in FIG.

(5) IR absorption spectrum The results measured in the KBr tablet are shown in FIG. (6) ¹ H-NMR spectrum The spectrum measured with deuterated chloroform at 400 MHz is shown in FIG.
As shown in. (7) Solubility Soluble in methanol, acetone, ethyl acetate and chloroform. Insoluble in n-hexane. (8) Color reaction Positive: Anisaldehyde sulfuric acid reaction, phosphomolybdic acid reaction, iodine reaction Negative: Ninhydrin reaction (9) Rf value of thin layer chromatography Silica gel plate F-254 (Merck) 0.12 (developing solvent) (Toluene: Acetone: Ammonia = 2: 1: 0.001) (10) Distinction between basic, neutral and acidic Basic

Further, the present invention provides Streptomyces (Strep
The present invention provides a method for producing an antibiotic, which comprises culturing a microorganism belonging to the genus tomyces) and having the ability to produce the antibiotics W7176B and W7176C, and collecting the antibiotic from the culture.

The microorganism used in the present invention belongs to the genus Streptomyces, and contains the antibiotic W7176B and
Any strain may be used as long as it has the ability to produce W7176C. For example, Me separated from the soil on the banks of the Hikiji River, Fujisawa City, Kanagawa Prefecture.
Examples of the r-W7176 strain include, but are not limited to this strain, belonging to the genus Streptomyces (Streptomyces), strains having the ability to produce the antibiotics W7176B and W7176C, including mutants thereof It can be used in the present invention.

The mycological properties of the Mer-W7176 strain will be described below. (1) Morphological properties Spiral aerial hyphae are elongated from well-branched basal hyphae. 10 to 50 ovals at the tip of mature aerial hyphae ~
It forms a spore chain consisting of cylindrical spores. No sporangia is observed. Spore size is 0.7-1.0 x 1.0-1.5 μm
The surface of the spores was smooth and no flagella were observed.

(2) Growth state in various media All cultures were performed at 28 ° C. Tone descriptions are available from Container Corpo of America.
(ration of America) Color Harmony Manual
It is displayed in parentheses by the code specified in (Color Harmony Manual). (2-1) Yeast / malt agar medium The growth of the basal mycelium is moderate, but the surface of the medium is wet and the development of aerial mycelia is unclear. The color of the basal hypha is almost cream-colored. The reverse side of the culture is colorless. No soluble dye is produced.

(2-2) Starch / inorganic salt agar medium The growth of basal hyphae is good, thin white aerial hyphae grow on the surface, and black gray (4li) spores are partially seen. .
The back surface is almost colorless, although some areas are blackish gray locally. No soluble dye is produced. (2-3) Tyrosine agar medium The growth of basal hyphae is moderate. It grows thin white aerial hyphae. It produces a melanin-like pigment in the medium.

(3) Assimilation of various carbon sources Various carbon sources were added to the Predham-Gotrieve agar medium, and growth was observed. (3-1) L-arabinose + (3-2) D-xylose + (3-3) D-glucose + (3-4) D-fructose + (3-5) sucrose + (3-6) inositol ＋ (3-7) L-rhamnose ＋ (3-8) Raffinose ＋ (3-9) D-mannitol ＋ Assimilate ＋,-do not assimilate

(4) Properties of cell wall components Hydrolyzed cells were analyzed by thin layer chromatography of cellulose, and the isomer form of diamino pimelic acid of the cell wall components of this bacterium was LL-type. The sugar component had no characteristics.

From the above mycological properties, it is clear that this bacterium is a bacterium of the genus Streptomyces, and International Journal of Systematic Bacteriology, Vol. 18, No. 2, 1968 (International Jou
(rnal of Systematic Bacteriology, vol.18, No.2, 1968)
In Streptomyces versciperis, when compared with the description properties of Streptomyces strains approved by the International Streptomyces Project,
(Streptomyces versipellis) was almost the same.

Therefore, the present inventors have designated the present strain as Streptomyces versipellis M.
er-W7176 and dated November 11, 1992 to the Institute of Microbial Science and Technology, the Agency of Industrial Science and Technology.
3273) was deposited.

The antibiotics W7176B and W7176C of the present invention are produced by inoculating the above strain into a nutrient medium and aerobically culturing. The method for culturing the above-mentioned strain is basically similar to the method for culturing general microorganisms, but it is usually preferable to carry out under aerobic conditions such as shaking culture by liquid culture and aeration and stirring culture.

The medium used for the culture may be any medium containing a nutrient source that can be utilized by microorganisms belonging to the genus Streptomyces, and various synthetic media,
Any of a semi-synthetic medium and a natural medium can be used. As the medium composition, glucose as a carbon source, sucrose, fructose, glycerin, dextrin, starch, molasses or the like can be used alone or in combination.

As the nitrogen source, it is possible to use pharmacological media, peptone, meat extract, soybean flour, casein, amino acids, yeast extract, organic nitrogen sources such as urea, inorganic nitrogen sources such as sodium nitrate and ammonium sulfate, alone or in combination. it can. In addition, salts such as sodium chloride, potassium chloride, calcium carbonate, magnesium sulfate, sodium phosphate, potassium phosphate and cobalt chloride, heavy metal salts, vitamins such as vitamin B and biotin can be added as required. . When foaming is remarkable during the culture, various known antifoaming agents can be appropriately added to the medium.

The culture conditions may be appropriately selected within a range in which the above strain can grow well and produce the antibiotics W7176B and W7176C. For example, the pH of the medium is preferably about 5 to 9, usually around neutral. The culture temperature is a temperature at which the microorganisms grow well, usually 20 to 40 ° C, preferably 28 to 35 ° C.
Better keep it at. The culture time may be about 2 to 8 days, preferably 3 to 5 days. Of course, the various culture conditions described above can be appropriately changed according to the type and characteristics of the microorganism used, external conditions, etc., and the optimum conditions can be selected and adjusted from the above range accordingly.

The accumulated amount of the antibiotics W7176B and W7176C in the culture can be quantified by an antibacterial activity assay by the disc diffusion method using, for example, Candida albicans as an assay bacterium. The antibiotics W7176B and W7176C accumulated in the above culture can be recovered by separating the bacterial cells by a general solid-liquid separation means such as filtration and centrifugation and extracting from the separated bacterial cells.

The antibiotics W7176B and W7176C can be separated and purified by selecting and combining various known methods. For example, ethyl acetate, solvent extraction using n-butanol and the like, Amberlite XAD (manufactured by Rohm and Haas Co.), polystyrene adsorption resin such as Diaion HP-20 (manufactured by Mitsubishi Kasei), silica gel, A method by column chromatography using a carrier such as alumina or activated carbon can be used.

The method of eluting the target substance from these carriers varies depending on the type and properties of the carrier. As an example, in the case of a polystyrene-based adsorption resin, hydrous alcohol, hydrous acetone or the like is used as the eluting solvent. it can. Furthermore, Sephadex LH-20 (Pharmacia), Bio-Gel P-2 (Bio-Rad), gel filtration, silica gel, thin-layer chromatography with alumina, etc. For example, preparative high performance liquid chromatography (preparative HPLC) can be used, and these methods can be separated or purified by using these methods individually or in an appropriate combination and, if necessary, repeatedly used.

The antibiotic W7176B obtained as described above
And W7176C have the following physicochemical properties. The physicochemical properties of the antibiotic W7176B of the present invention are as follows. (1) Appearance: White powder (2) High-resolution FAB mass spectrum Measured value: 912.6055 Calculated value: 912.6048 (as C ₄₉ H ₈₆ O ₁₄ N) (3) FAB mass spectrum (matrix; m-nitrobenzyl alcohol) m / z; 912 (M + H) ⁺ (4) Molecular formula: C ₄₉ H ₈₅ O ₁₄ N

(5) Optical rotation [α] ²⁷ _D -15 ° (C = 0.5, methanol solution) (6) UV absorption spectrum The result measured with a methanol solution is as shown in FIG. 1, and the maximum absorption is as follows. As shown in. λ _max : 212 nm (ε 11700) (8) IR absorption spectrum The result measured in the KBr tablet is as shown in FIG.
The characteristic absorption is as shown below. ν _max : 3476,2940,1717,1647cm ^-1

(9) ¹ H-NMR spectrum The result measured in a heavy chloroform solution at 400 MHz is shown in FIG.
And the clear absorption is as shown below. (CDCl ₃ , δ) 6.84 (1H, dd, J = 1Hz, 15.5Hz), 6.17 (1H, d, J = 15.5Hz), 5.22
(1H, s), 4.84 (1H, dd, J = 3Hz, 8Hz), 4.36 (1H, d, J = 12Hz), 4.
14 (1H, t, J = 11Hz), 4.03 (1H, d, J = 8Hz), 3.82 (1H, s), 3.76 (1
H, d, J = 8Hz), 3.39 (1H, s), 3.15 (1H, s), 2.99 (1H, d, J = 10H
z), 2.69 (1H, s), 2.25 (6H, s), 1.42 (3H, s), 1.35 (3H, s), 1.2
9 (3H, d, J = 6.5Hz), 1.25 (3H, s), 1.14 (3H, s), 0.98 (3H, t, J =
7.5Hz), 0.89 (3H, d, J = 7Hz), 0.77 (3H, d, J = 7Hz)

(10) ¹³ C-NMR spectrum The result measured at 100 MHz in a heavy chloroform solution is shown in FIG.
And the clear absorption is as shown below. (CDCl ₃ , δ) 164.7s, 148.7d, 133.7d, 129.1d, 119.3d, 106.1s, 98.4d, 9
8.2s, 86.1d, 81.6s, 79.4d, 77.3d, 74.7s, 74.7s, 74.4d, 72.
3d, 69.6d, 68.0d, 67.8d, 65.6d, 61.9d, 54.2d, 44.0t, 43.3
q, 43.3q, 43.1t, 40.0t, 38.3t, 35.6d, 35.4t, 34.4d, 34.1t,
32.5t, 30.8t, 30.3q, 30.3t, 30.0t, 29.7t, 29.1t, 28.9q, 2
8.6q, 23.5t, 22.2q, 20.0t, 19.3t, 13.4q, 10.0q, 6.0q, 5.6q

(11) Solubility Soluble in methanol, acetone, ethyl acetate and chloroform. Insoluble in n-hexane. (12) Color reaction Positive: Anisaldehyde sulfuric acid reaction, phosphomolybdic acid reaction, iodo reaction Negative: Ninhydrin reaction (13) Rf value of thin layer chromatography 0.28 with silica gel plate F-254 (Merck)
(Developing solvent toluene: acetone: ammonia = 2: 1: 0.00
1) (14) Distinction between basic, neutral and acidic Basic

The physicochemical properties of the antibiotic W7176C of the present invention are as follows. (1) Appearance: White powder (2) FAB mass spectrum (matrix; m-nitrobenzyl alcohol) m / z; 894 (M + H) ⁺ (3) Molecular formula: C ₄₉ H ₈₃ O ₁₃ N (4) UV absorption Spectrum The results of measurement with a methanol solution are as shown in FIG. 5, and the maximum absorptions are as shown below. λ _max : 214nm, 257nm

(5) IR absorption spectrum: The result measured in the KBr tablet is as shown in FIG. 6, and the characteristic absorption is shown below. ν _max : 3437,2934,1718,1460,1383,1269cm ^-1 (6) ¹ H-NMR spectrum The result measured at 400 MHz in deuterated chloroform solution is shown in FIG.
, And the clear absorption is as follows: (CDCl3, δ) 6.79 (1H, d, J = 1Hz, 16Hz), 6.11 (1H, d, J = 16Hz), 2.24 (6H,
s), 1.00 (3H, t, J = 7.5Hz), 0.88 (3H, d, J = 7Hz), 0.81 (3H, d, J
= 7Hz)

(7) Solubility Soluble in methanol, acetone, ethyl acetate and chloroform. Insoluble in n-hexane. (8) Color reaction: Positive: Anisaldehyde sulfuric acid reaction, phosphomolybdic acid reaction, iodine reaction Negative: Ninhydrin reaction (9) Rf value of thin layer chromatography: 0.12 (on silica gel plate F-254 (Merck)) Developing solvent Toluene: Acetone: Ammonia = 2: 1: 0.001) (10) Distinction between basic, neutral and acidic Basic

The antibiotics W7176B and W7176C of the present invention are
Candida albicans (Can
dida albicans), Aspergis fumigatus (Aspergi
(llus fumigatus) and the like are suppressed at low concentrations. Next, the minimum inhibitory concentration (MIC, μg / ml) of the antibiotics W7176B and W7176C of the present invention against pathogenic fungi was measured by the micro liquid dilution method and the results are shown in Table 1. Mueller Hinton medium was used for bacteria and Sabouraud dextrose medium was used for fungi, and MIC (minimum inhibitory concentration) was determined after 48 hours at 30 ° C.

[0035]

[Table 1]

As is clear from Table 1, the antibiotic W7176B
And W7176C is Candida
The growth of Albicans (Candida albicans) and Aspergillus fumigatus was suppressed at low concentrations. Antibiotics W7176B and W7176C substances can be made into tablets, powders, capsules, injections, inhalants, external preparations, etc. by a conventional method, and can be clinically used as antifungal agents by oral or parenteral administration. it can. The dose may be appropriately selected depending on the symptom to be treated and the administration method, for example, 100 to 1000 mg per day for an adult, preferably
200 to 600 mg should be administered.

[0037]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. The percentage (%) in the medium indicates weight / volume percentage unless otherwise specified.

Example 1 Production of Antibiotic W7176B From a slant medium (ISP-2 agar medium) of Mer-W7176 strain to seed medium
(2% potato starch, 2% glucose, 2% soybean flour,
Yeast extract 0.5%, sodium chloride 0.25%, calcium carbonate 0.32%, adjusted to pH 7.4 before heat sterilization) 50ml included 5
One platinum loop was inoculated into nine 00 ml Erlenmeyer flasks and cultured at 28 ° C for 3 days on a rotary stirrer to obtain a seed culture solution.

300 ml of each of the seed cultures was used as a production medium (galactose 2%, dextrin 2%, bactosoyton 1%,
Corn steep liquor 0.5%, ammonium sulfate
0.2%, calcium carbonate 0.2%, pH 7.4) 0.05% antifoaming agent Adecanol (trade name: Asahi Denka Kogyo)
Three 10-liter jar fermenters containing 5 liters were inoculated, respectively, and aerated and agitated culture (aeration rate 5 liter / min, agitation 300 rpm) was performed at 28 ° C. for 88 hours.

After completion of the culture, the bacterial cells were collected from about 15 liters of the culture solution by filtration. 7 L of methanol was added to the cells thus obtained, and the target substance was extracted while stirring with a stirrer for 1 hour. After removing the bacterial cells by filtration, the methanol extract was concentrated under reduced pressure to distill off methanol. 1 liter of water was added to the obtained residue, and ethyl acetate was added to 500
Extraction was performed 3 times with ml. The ethyl acetate extracts were combined and concentrated to dryness to obtain 2.5 g of tar-like substance.

The whole amount was dissolved in 13 ml of methanol and applied to a Sephadex LH-20 column (manufactured by Pharmacia, 4.5φ × 45 cm) preliminarily filled with methanol, developed with methanol, and collected in 12 g portions. Detected by the antibacterial assay shown below, the active fractions 12 to 20 were collected and concentrated to dryness to obtain 798 mg of a concentrate.

This concentrate was dissolved in a mixed solution of toluene: acetone = 1: 1 and attached to a silica gel column (Silica gel 60 Art.7734 (Merck), 2.2φ × 45 cm) pre-filled with a solvent having the same composition as this solution. And elute with the same solvent, 6g
We collected each. Antibacterial activity and silica gel thin layer chromatography (Art.5715 (Merck), developing solvent: toluene:
Active fractions were detected with (acetone: ammonia = 2: 1: 0.001, detection: iodine coloration), and fractions 39 to 100 were collected and concentrated to dryness to obtain 150 mg of a concentrate. The antibacterial assay was performed by the Candida albicans assay plate method.

This was heated at a temperature of 25 ° C., a rotation speed of 500 rpm, a solvent (hexane: ethyl acetate: methanol: water = 8: 2: 5: 5), and a flow rate of 4 m
Centrifugal partition chromatography was performed under the condition of l / min. 6
The fractions were separated by ml and detected under the same conditions as in the silica gel thin layer chromatography described above. The upper layer of the solvent was developed as a mobile phase, and fractions 14 to 30 were collected and concentrated to obtain 45 mg of the white antibiotic W7176B.

Example 2 Production of Antibiotic W7176C Silica gel column chromatography in Example 1
(Silica gel 60 Art.7734 (Merck), 2.2φ x 45 cm) Fractions 101 to 180 were collected, concentrated to dryness, and concentrated to 50 mg.
Got

This was subjected to centrifugal partition chromatography under the same conditions as in Example 1. After development, it was re-eluted with a fixed bed solvent, and 6 ml each was collected. The obtained fractions 9 to 14 were collected and concentrated to obtain 4 mg of white antibiotic W7176C.

[0046]

EFFECT OF THE INVENTION Antibiotics of the present invention W7176B and W7176C
As shown in Table 1, has an antifungal activity against Candida albicans and Aspergillus fumigatus, which are fungi causing fungi. Based on these properties, the antibiotics W7176B and W7176C of the present invention are expected to be used as medicines, agricultural chemicals or materials for converting them.

[0047]

[Brief description of drawings]

FIG. 1 shows an ultraviolet absorption spectrum of antibiotic W7176B in methanol.

FIG. 2 shows an infrared absorption spectrum of antibiotic W7176B by the KBr method.

Figure 3: 40 of antibiotic W7176B in deuterated chloroform solution
The 0 MHz ¹ H-NMR spectrum is shown.

Figure 4: Antibiotic W7176B 10 in deuterated chloroform solution
The 0 MHz ¹³ C-NMR spectrum is shown.

FIG. 5 shows an ultraviolet absorption spectrum of antibiotic W7176C in methanol.

FIG. 6 shows an infrared absorption spectrum of antibiotic W7176C by the KBr method.

FIG. 7: Antibiotic W7176C 40 in deuterated chloroform solution
The 0 MHz ¹ H-NMR spectrum is shown.

Front page continuation (72) Inventor Rokuro Okamoto 2-18 Hanaki, Fujisawa City, Kanagawa Prefecture (72) Inventor Satoshi Mizuno 1-23-1 Toyama, Shinjuku-ku, Tokyo National Institute of Preventive Health and Welfare

Claims (4)

[Claims] 1. An antibiotic W7 having the following physicochemical properties:
176B. (1) Appearance: White powder (2) High resolution FAB mass spectrum m / z: 912.6055 (M + H) ⁺ (3) FAB mass spectrum (matrix; m-nitrobenzyl alcohol) m / z; 912 (M + H) ) ⁺ (4) Molecular formula: C ₄₉ H ₈₅ O ₁₄ N (5) Optical rotation [α] ²⁷ _D -15 ° (C = 0.5, methanol solution) (6) UV absorption spectrum It is as shown in 1. (7) IR absorption spectrum The result measured in the KBr tablet is as shown in FIG. (8) ¹ H-NMR spectrum The spectrum measured with deuterated chloroform at 400 MHz is shown in FIG.
As shown in. (9) ¹³ C-NMR spectrum The spectrum measured at 100 MHz in deuterated chloroform is shown in FIG.
As shown in. (10) Solubility Soluble in methanol, acetone, ethyl acetate and chloroform. Insoluble in n-hexane. (11) Color reaction Positive: Anisaldehyde sulfuric acid reaction, phosphomolybdic acid reaction, iodine reaction Negative: Ninhydrin reaction (12) Rf value of thin layer chromatography 0.28 with silica gel plate F-254 (Merck) (developing solvent) (Toluene: Acetone: Ammonia = 2: 1: 0.001) (13) Distinction between basic, neutral and acidic Basic 2. An antibiotic W7 having the following physicochemical properties.
176C. (1) Appearance: White powder (2) FAB mass spectrum (matrix; m-nitrobenzyl alcohol) m / z; 894 (M + H) ⁺ (3) Molecular formula: C ₄₉ H ₈₃ O ₁₃ N (4) UV absorption Spectrum The result of measurement with the methanol solution is as shown in FIG. (5) IR absorption spectrum The result measured in the KBr tablet is as shown in FIG. (6) ¹ H-NMR spectrum The spectrum measured with deuterated chloroform at 400 MHz is shown in FIG.
As shown in. (7) Solubility Soluble in methanol, acetone, ethyl acetate and chloroform. Insoluble in n-hexane. (8) Color reaction Positive: Anisaldehyde sulfuric acid reaction, phosphomolybdic acid reaction, iodine reaction Negative: Ninhydrin reaction (9) Rf value of thin layer chromatography Silica gel plate F-254 (Merck) 0.12 (developing solvent) (Toluene: Acetone: Ammonia = 2: 1: 0.001) (10) Distinction between basic, neutral and acidic Basic 3. A method for producing the antibiotic W7176B, which comprises culturing an antibiotic W7176B-producing bacterium belonging to the genus Streptomyces and collecting the antibiotic W7176B from the culture. 4. A method for producing an antibiotic W7176C, which comprises culturing an antibiotic W7176C-producing bacterium belonging to the genus Streptomyces and collecting the antibiotic W7176C from the culture.