JPH0538283A - New microorganism - Google Patents

Abstract

PURPOSE:To obtain a new microorganism capable of hydroxylating an M-236B derivative separated from a metabolite of Penicillium citrinum and providing a compound capable of exhibiting inhibitory action on cholesterol synthesis. CONSTITUTION:A new strain Streptomyces carbophilus, preferably Streptomyces carbophilus SANK62585 (FERM P-1145) having grayish white to bright olive gray to light yellowish orange aerial hyphae adhering onto light yellowish orange to light brown to bright olive gray basal hyphae, straight or curved or rarely helical spore chains and smooth spore surfaces and well growing even on a Pridham.Godlieb control culture medium without any carbon source added thereto and having the ability to hydroxylate a compound expressed by formula I into a compound expressed by formula II. The aforementioned microorganism is obtained by diluting soil obtained from Canberra City in Australia with sterile water, culturing the soil in an agar culture medium for separation and separating the microorganism from the resultant colony of the actinomyces.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION

[0002]

[Chemical 1]

A carboxylic acid having, a pharmacologically acceptable salt thereof, an ester thereof or a ring-closed lactone thereof.
The ML-236B derivative can be represented, for example, by the formula

[0004]

[Chemical 2]

Carboxylic acid having, a pharmacologically acceptable salt thereof, an ester thereof or a ring-closing lactone thereof (hereinafter, referred to as
Collectively referred to as "3", 6'-dihydroxy-ML-236B derivative ". ) To a novel microorganism having a hydroxylation ability.

[0006]

2. Description of the Related Art Conventionally, ML-236 having the above general formula (I)
Streptomyces roseochromogenas is known as a microorganism belonging to the genus Streptomyces that hydroxylates a B derivative and converts it into the derivative (JP-A-57-50894).
issue).

[0007]

DISCLOSURE OF THE INVENTION The present inventors have, for example,
The ML-236B derivative was converted to 3 ", 6'-dihydroxy-ML-236
We have discovered a novel microorganism with hydroxylation ability that can be converted to a B derivative, as well as 3 ", 6'-dihydroxy-ML-236B.
The present inventors have completed the present invention by discovering that all the derivatives exhibit a cholesterol synthesis inhibitory action.

Examples of the pharmacologically acceptable salt of the compound represented by the general formula (II) of the present invention include metal salts, amino acid salts and amine salts. Examples of the metal salt include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, and aluminum salts, iron salts, zinc salts, copper salts, nickel salts and cobalt salts. Medium, alkali metal salts, alkaline earth metal salts and aluminum salts are preferred,
Furthermore, sodium salts, potassium salts, calcium salts and aluminum salts are most preferred. As the amino acid salt, for example, basic amino acids such as arginine, lysine, histidine, α, γ-diaminobutyric acid, ornithine are suitable. Examples of amino salts include t-octylamine, dibenzylamine, dicyclohexylamine, morpholine,
D-phenylglycine alkyl ester, D-glucosamine and the like are preferable.

Examples of the ester of the compound having the general formula (II) include alkyl esters such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and pentyl. Preferred is methyl.

The ring-closed lactone form of the compound having the general formula (II) means a compound in which the formula (II) is represented by the following ring-closed structural formula.

[0011]

[Chemical 3]

Examples of the 3 ", 6'-dihydroxy-ML-236B derivative obtained by the present invention include the compounds described below.

1) 3 ", 6'-dihydroxy-ML-236B carboxylic acid 2) 3", 6'-dihydroxy-ML-236B carboxylic acid sodium salt 3) 3 ", 6'-dihydroxy-ML-236B carboxylic acid Potassium salt 4) 3 ", 6'-dihydroxy-ML-236B carboxylic acid calcium salt 5) 3", 6'-dihydroxy-ML-236B carboxylic acid aluminum salt 6) 3 ", 6'-dihydroxy-ML-236B carvone Acid arginine salt 7) 3 ", 6'-dihydroxy-ML-236B carboxylic acid lysine salt 8) 3", 6'-dihydroxy-ML-236B carboxylic acid t
-Octylamine salt 9) 3 ", 6'-dihydroxy-ML-236B carboxylic acid D
-Phenylglycine ethyl ester salt 10) 3 ", 6'-dihydroxy-ML-236B carboxylic acid methyl ester 11) 3", 6'-dihydroxy-ML-236B lactone form.

In the above general formula (II), various geometric isomers exist depending on the arrangement of substituents. Also, various optical isomers exist due to the presence of asymmetric carbon atoms. In the general formula (II), these isomers and mixtures of these isomers are all represented by a single formula. Therefore, in the present invention, the carboxylic acid having the general formula (II), a pharmacologically acceptable salt thereof, an ester thereof or a ring-closing lactone thereof is not limited to these isomers,
It also includes all mixtures of these isomers.

The 3 ", 6'-dihydroxy-ML-236B derivative has an action of lowering lipids in the blood by inhibiting the synthesis of cholesterol. For example, it is used as a therapeutic agent for hyperlipidemia and an agent for preventing arteriosclerosis. It can be used in medicine.

These compounds can be administered orally or parenterally in the form of capsules, tablets, injections and the like. The dose varies depending on the age, symptoms, body weight, etc., but is usually about 0.2 to 200 mg daily for adults to 3 to 4 mg.
It is administered in divided doses. However, higher amounts can be used if desired.

The starting materials of the present invention, such as ML-236B lactone and ML-236B carboxylic acid, are known materials as described above, and are separated and purified from the metabolite of Penicillium citrinum, a kind of blue mold. Its chemical structural formula is

[0018]

[Chemical 4]

And

[0020]

[Chemical 5]

Inhibiting cholesterol biosynthesis in an enzyme system or a cultured cell system isolated from an experimental animal by competing with its rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase. However, it is known to exhibit a strong serum cholesterol lowering effect even at the individual level of animals (Japanese Patent Laid-Open No. 50-155690; Atherosclerosis).
s), 32, 307-313, 1979).

[0022]

The novel microorganisms of the present invention have, for example, the formula

[0023]

[Chemical 6]

A carboxylic acid having, a pharmacologically acceptable salt thereof, an ester thereof or a ring-closed lactone thereof.
The ML-236B derivative has a hydroxylation ability that can be hydroxylated to be converted into a 3 ″, 6′-dihydroxy-ML-236B derivative. Such novel microorganisms include those belonging to the genus Streptomyces.

Among the microorganisms belonging to these, especially Streptomycec sp. SANK 62585
(Microtechnical Laboratory Article 1145 (FERM BP-1145)) is preferable.

Streptomyces sp. SANK 62585
The mycological properties of the strain are as follows. 1. Morphological Features Morphology is ISP [International Streptomyces Proje
ct)] After culturing on a defined medium at 28 ° C for 14 days, the cells were observed under a microscope. The basal hyphae of the SANK 62585 strain are well branched and elongated, and the aerial hyphae are simple branches.

The spore chains of the SANK 62585 strain are usually straight to curved, but sometimes have a spiral shape. The surface structure of the spore chains is smooth. Axial branch of aerial mycelium,
No special organs such as sclerotia, disruption of basal hyphae, sporangia were observed.

2. Various properties on various culture media Table 1 shows the properties after culturing on various culture media at 28 ° C for 14 days. The display of the color tone indicates the color chip number of the "Standard Color Chart" of the Japan Color Research Institute version.

[0029]

[Table 1]

3. Physiological Properties Physiological properties of SANK 62585 strain are shown in Table 2.

[0031]

[Table 2] Properties of SANK 62585 strain ────────────────────────── Starch hydrolysis positive gelatin liquefaction negative nitrate reduction positive milk coagulation Positive Peptone conversion of milk Positive Growth temperature range (medium 1) ^* 4 to 45 ° C Optimal growth range (medium 1) 15 to 35 ° C Melanin-like pigment producing area (medium 2) Negative (medium 3) False positive ^** (medium 4) ) Negative ────────────────────────── *: Medium 1; Yeast extract: Malt extract agar (ISP2) 2; Tryptone, yeast extract, broth (ISP1) 3; Peptone / Yeast extract / Iron agar (ISP6) 4; Tyrosine agar (ISP7) **: A melanin-like pigment may be produced in the latter stage of culture.

Further, using a Prideham-Gortribe agar medium, carbon sources after 14 days of culturing, that is, D-glucose, L-arabinose, D-xylose, inositol, D-mannitol, D-fructose, L-rhamnose, The utilization of sucrose, raffinose, cellobiose and trehalose was investigated. The SANK 62585 strain grows well even in a control medium containing no carbon source, so it is difficult to describe its exact assimilation ability. However,
In the medium supplemented with D-glucose, D-xylose, inositol, raffinose, cellobiose, and trehalose, remarkably good growth was observed as compared with the control medium without addition.

4. About the bacterial cell components The cell wall of the SANK 62585 strain is the method of Becker et al. [B.
Becker et al., Applied Microbiology (Ap
plied Microbiology), vol. 12, 421-423, 1964
Years], L, L-diaminopimelic acid and glycine were detected.
Was confirmed. In addition, the sugar component in the whole cells of the SANK 62585 strain was analyzed by the method of MP Reschevarier [MPLe
chevalier, Journal of Laboratory and
Clinical Medicine (Journal of Laboratory and C
linical Medicine), 71, 934, 1968], and no characteristic pattern was observed.
From the above, it was revealed that this strain belongs to the genus Streptomyces among actinomycetes.

The SANK 62585 strain was identified by the ISP [The International Streptomyces Project] standard: Bergey's Manual of Det.
erminative Bacteriology, 8th edition; by SA Waksman, The Actinomycetes, Vol. 2 and recent literature on actinomycetes.

As a result, this strain was judged to be a new species of the genus since it did not correspond to any of the known Streptomyces species, and Streptomyces carbophils (Stre
ptomyces carbophilus) SANK 62585 (Deposit organization, Institute of Microbial Science and Technology, Agency of Industrial Science and Technology: Deposit number, Microtechnology Research Institute No. 11
No. 45 (FERM BP-1145): Original deposit date, September 5, 1985).

Next, a method for separating the new strain of the present invention from soil will be described. The new strain of the present invention is isolated by a conventional method. That is, the soil collected from the city of Canberra, Australia, was appropriately diluted with sterile water prepared in advance, then smeared on a separation agar medium TA having the composition shown below, and cultured by culturing at 28 ° C for 10 days. This strain can be isolated from the incoming actinomycete colonies.

TA medium trehalose 10 g L-asparagine 1 g K ₂ HPO ₄ 0.5 g ISP trace salt solution 1 g nystatin 0.025 g agar 20 g distilled water 1000 ml・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ PH 7.0.

The medium used for separating from the new bacterial species of the present invention may be a synthetic or natural medium as long as it contains an appropriate amount of one selected from a carbon source, a nitrogen source, an inorganic ion and an organic nutrient source. Either can be used.

The SANK 62585 strain has been described above.
It is well known that the properties of actinomycetes are not constant, and easily change naturally and artificially. The strain of the present invention belongs to Streptomyces carbophilus, and ML-2
It includes all strains capable of converting 36B derivatives into 3 ", 6'-dihydroxy-ML-236B derivatives.

When carrying out using the novel microorganism of the present invention, the method for enzymatically hydroxylating is as follows. The converting bacterium is cultured under a culture condition suitable for its growth, and a) the starting compound is added to the medium. Contact method, b) culturing and collecting the transformed bacteria, and bringing the obtained transformed bacterial cells into contact with the starting compound, and c) contacting the cell-free extract prepared from the transformed bacterial cells with the starting compound The method of making it adopted is adopted.

As a method of culturing the converted bacterium, it can be usually cultivated in a medium containing a nutrient that can be utilized by the microorganism. As a nutrient source, a known one used in general microbial culture can be used. For example, glucose, sucrose, starch, glycerin, starch syrup, molasses, soybean oil and the like can be used as the carbon source. As the nitrogen source, soybean flour, wheat germ, meat extract, peptone, corn steep liquor, dried yeast, ammonium sulfate and the like can be used. In addition to inorganic salts such as sodium chloride, potassium chloride, calcium carbonate, and phosphate, if necessary, it is possible to appropriately combine and use additives necessary for promoting the growth of bacteria and promoting the production of the enzyme having hydroxylation ability. it can. As a culturing method, a culturing method generally used for microorganisms, for example, a liquid culturing method is possible, and a submerged culturing method is industrially suitable.

The culture is carried out under aerobic conditions and the culture temperature is
It is 20 to 37 ° C, preferably 26 to 35 ° C.

The method a) is carried out by adding a starting compound and culturing. Although the timing of addition varies depending on the optimal culture conditions for the converting bacteria to be used, especially the culture equipment, medium composition, culture temperature, etc., the time at which the hydroxylating ability of the converting bacteria begins to increase is good. It is preferable that ~ 3 days have passed. The amount of raw material compound added is 0.01-
It is selected from the range of 5.0%, preferably 0.05 to 2.0%. Cultivation after the addition of the raw material compounds is carried out under the aerobic conditions at the above-mentioned culture temperature. Cultivation period is after addition of raw material compounds
3-5 days.

In the method b), the converting bacterium is cultured in the presence of a small amount of the substrate by the above-mentioned method and cultivated until the hydroxylating ability of the converting bacterium becomes maximum. That is, although the hydroxylation capacity varies depending on the type of medium, temperature, etc., it usually reaches its maximum in 4 to 5 days after the start of culture, so the culture is terminated at this point. The bacteria are collected by subjecting the culture to methods such as centrifugation and filtration. It is preferable that the collected transformed bacterial cells are usually washed with physiological saline, a buffer solution or the like before use.

In order to bring the converted bacterial cells thus obtained into contact with the starting compound, usually, in an aqueous medium, for example, p.
Performed in H 5-9 phosphate buffer. Reaction temperature is 2
The temperature is 0 to 45 ° C, preferably 25 to 35 ° C. The concentration of the raw material compound is usually selected from the range of 0.01 to 5.0%. The reaction time depends on the concentration of raw material compounds, reaction temperature, etc., but is usually 1
~ 5 days.

The cell-free extract obtained by the method c) is treated as a cell disruption product by applying physical or chemical means to the transformed bacterial cells obtained by the above method, for example, grinding or sonication. Alternatively, it can be obtained as a cell lysate by treatment with a surfactant or an enzyme. The method of contacting the cell-free extract thus obtained with the starting compound is performed in the same manner as the method of contacting the converted bacterial cells with the starting compound.

After completion of the conversion reaction, the target compound can be directly collected, separated and purified from the product by a known method.
For example, the product is filtered, the resulting filtrate is extracted with an organic solvent that is immiscible with water, such as ethyl acetate, the solvent is distilled off from the extract, and the resulting crude target compound is silica gel, alumina, etc. Attached to a column chromatograph using
It can be separated and purified by eluting with an appropriate eluent.

Further, the obtained product can be converted into a target compound by subjecting it to hydrolysis, salt formation reaction, esterification reaction or lactonization reaction according to a conventional chemical method, and can be easily collected. ..

All of these methods are conventional methods, for example, the following methods. The carboxylic acid having the formula (II) can be obtained by adjusting the obtained filtrate to pH 4 or less, preferably pH 3 to 4, when the product of the conversion reaction is a carboxylate. The acid used is not limited to organic acids or mineral acids as long as it does not affect the target compound, and trifluoroacetic acid, hydrochloric acid, sulfuric acid, etc. are preferably used.

The carboxylic acid thus obtained can be used in the following reaction after being subjected to treatments such as extraction, washing and dehydration.

The metal salt of a carboxylic acid having the formula (II) is
It is obtained by contacting the metal hydroxide, carbonate or the like with the carboxylic acid in an aqueous solvent. As the aqueous solvent to be used, for example, water; alcohols such as methanol and ethanol, a mixed solvent of water and an organic solvent such as acetone, n-hexane, and ethyl acetate are preferable. A mixed solvent of a hydrophilic organic solvent and water is particularly preferable. The reaction is usually carried out preferably near room temperature, but may be carried out under heating if necessary.

The amine salt of a carboxylic acid having the formula (II) is obtained by contacting an amine with the above carboxylic acid in an aqueous solvent. Examples of the aqueous solvent used include water; alcohols such as methanol and ethanol,
Examples thereof include ethers such as tetrahydrofuran, mixed solvents of water and nitriles such as acetonitrile, and the like, and water-containing acetone is preferable. The reaction is usually p
It is preferably carried out at H7 to 8.5 and below room temperature, especially at 5 to 10 ° C. The reaction is instantly complete. Alternatively, for example, it can be obtained by a salt exchange reaction by dissolving the carboxylic acid metal salt obtained above in an aqueous solvent, and then adding a mineral acid salt (for example, hydrochloride) of the target amine under the above conditions.

The amino acid salt of a carboxylic acid having the formula (II) can be obtained by contacting an amino acid with the above carboxylic acid in an aqueous solvent. Examples of the aqueous solvent used include water; alcohols such as methanol and ethanol; mixed solvents of ethers such as tetrahydrofuran and water; and the like. The reaction is usually performed under heating, preferably at about 50-60 ° C.

The alkyl ester of carboxylic acid having the formula (II) is obtained by contacting the carboxylic acid obtained above with an alcohol. At this time, a mineral acid such as hydrochloric acid, sulfuric acid or the like, boron fluoride, an acidic ion exchange resin or the like is used as the catalyst, and the same alcohol or benzene, chloroform, ether or the like which does not participate in the reaction is used as the solvent. Alternatively, it can be obtained by contacting the carboxylic acid obtained above with a diazoalkane. The reaction is usually carried out by contacting with a solution of diazoalkane in ether. Alternatively, it can be obtained by contacting the metal salt of the carboxylic acid obtained above with an alkyl halide. Examples of the solvent used include dimethylformamide, tetrahydrofuran,
Dimethyl sulfoxide, acetone and the like are preferable. Although all the reactions are preferably carried out near room temperature, they may be carried out under heating, if necessary, depending on the type of reaction system.

The lactone form of the carboxylic acid having the formula (II) can be obtained by contacting the carboxylic acid obtained above with a catalytic amount of acid. The acid used is preferably an organic acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid, or a mineral acid. The reaction is usually suitably carried out near room temperature.

Further, the target compound thus obtained can be used as a raw material and converted into another target compound according to the above-mentioned conventional chemical method.

The 3 ", 6'-dihydroxy-ML-236B derivative thus obtained can be collected, separated and purified by appropriately combining various methods.
For example, it is carried out by adsorption or ion exchange chromatography using various carriers such as activated carbon and silica gel, gel filtration using a Sephadex column, extraction with an organic solvent such as ether, ethyl acetate and chloroform.

Separation of isomers can be carried out by the above-mentioned separation and purification means at an appropriate time after completion of the conversion reaction or after completion of the desired step.

[0059]

EXAMPLES Next, examples and reference examples will be shown, but the present invention is not limited thereto.

Example 1. Isolation of Streptomyces carbophilus, a new bacterial species 1 g of soil and soil-adhered plant pieces collected from Canberra, Australia, were suspended in 9 ml of sterilized water, thoroughly stirred with a mixer, and then left for about 30 minutes. 1 ml of the soil suspension supernatant thus obtained was diluted 1000-fold, and 0.05 ml of the supernatant was smeared on a separation agar medium TA having the composition shown below using a sterile conradi stick.
These agar media were cultured at 28 ° C for 10 days.

Composition of agar medium TA for separation trehalose 10 g L-asparagine 1 g K ₂ HPO ₄ 0.5 g ISP trace salt solution 1 g nystatin 0.025 g agar 20 g distilled water 1000 ml ・ ・ ・ ・ ・ ・ ・ ・ ・ ・··· pH 7.0.

Streptomyces carbophilus (Stre
ptomycescarbophilus) SANK 62585
No. (FERM BP-1145)) TA prepared as described above
The colonies that appeared on the agar medium were inoculated into a yeast malt agar (ISP2) slope medium and cultured at 28 ° C for 14 days. It was confirmed that this strain was a single strain by monocolony treatment or the like. Alternatively, the strain cultured as described above can be stored as a freeze-dried ampoule prepared using 10% skim milk as a dispersant.

Reference Example 1.3 3 "α, 6'β-dihydroxy-ML-236B carboxylic acid sodium salt (substance B) and
3 "β, 6'β-Dihydroxy-ML-236B Carboxylic Acid Sodium Salt (Substance A)

[0064]

[Chemical 7]

500 m containing 100 ml of medium having the following composition
Streptomyces carbophilus SANK 62585 strain was inoculated into 20 Erlenmeyer flasks and heated at 27-28 ℃, 220 r.
Culture was performed with shaking at pm. After 2 days, add ML-236B carboxylic acid sodium salt to a final concentration of 0.05%,
The cells were further cultured for 5 days at 27 to 28 ° C and 220 rpm.

Medium composition Glucose 2.0% Peptone 1.0 Yeast extract 0.1 Tap water residue (pH 7.0).

After completion of the culture, the conversion reaction solution was filtered, and the filtrate was adjusted to pH 8.5 with caustic soda. Next, the filtrate was applied to a column packed with 600 ml of high-porous polymer HP-20, washed with 3600 ml of water, and then eluted with 1200 ml of 20% v / v methanol.

The eluate was concentrated under reduced pressure and then freeze-dried to give a solid product.
720 mg was obtained. Liquid chromatography for preparative analysis of this solid (used column SSC-ODS-2942, φ 30 mm × 250
mm) and repeated elution was carried out using 30% v / v methanol as a developing solvent to obtain a first eluting substance A and then a second eluting substance B. Each of the two substances obtained here was concentrated under reduced pressure and then freeze-dried to give 45 mg of pure substance A.
And 38 mg of substance B were obtained.

The physical properties of substances A and B are as follows. 1) Molecular formula: C ₂₃ H ₃₅ O ₈ Na 2) Molecular weight: As a result of measurement by FAB-MS method, both substance A and substance B are 463 (M + H) ⁺ and 485 (M + Na) ⁺
Met. 3) High performance liquid chromatography: Substance A has a retention time of 4.833 minutes and substance B has a retention time of 5.5 minutes under the following conditions. Column; ERC-ODS-1262 with an inner diameter of about 6 mm and a length of about 10 cm
(Manufactured by Elmer Optical Co., Ltd.) Mobile phase: methanol: water: glacial acetic acid: triethylamine (5
00: 500: 1: 1) Column temperature; 40 ° C Flow rate; 1.0 ml / min Detector; UV 238 nm 4) Gas chromatography: B substance is 2 under the following conditions.
4.563 minutes, material A has a retention time of 25.475 minutes. Column; inner diameter about 0.2 mm, length about 25 m, film thickness 0.33 μ
m chemically bonded methyl silicon (manufactured by Hewlett-Packard Company, ULTRA # 1) Column temperature: about 280 ℃ Sample vaporization chamber and detector temperature; Approx. 300 ℃ Carrier gas; Helium 2.0 ml / min Detector; Hydrogen flame ionization detection vessel

[0070]

【The invention's effect】

Test Example 1. Cholesterol synthesis inhibitory action 3 ″, 6 ′ β-dihydroxy-ML-236B derivative is a 3-hydroxy-3-methylglutaryl coenzyme A reductase (3-hydroxy-3-methyl-) which is known as a rate-limiting enzyme in the cholesterol synthesis pathway. gluaryl −Co Ar
It was found that it specifically inhibits eductase). Cholesterol synthesis inhibitory action of these compounds [Journal of Biological Chemistry (J. Biol. Chem.),
234, page 2835 (1959).

[0071]

[Table 3] Concentration that inhibits cholesterol synthesis by 50% ・ ・ ・ ・ ・ ・ ・ ・ μg / ml ・ ・ ・ ・・ ・ ・ ・ A substance 0.0018 B substance 0.024 ML-236B Lactone (control) 0.010 ・ ・ ・ ・...........

Continuation of the front page (51) Int.Cl. ⁵ Identification code Reference number within the agency FI Technical display part (C12P 17/06 C12R 1: 465) (C12P 7/42 C12R 1: 465) (C12P 7/62 C12R 1: 465) (72) Inventor Jun Yoshikawa, 1-2-5, Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor, Toshiaki Iwai 1-2-5-2, Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Kunio Nakano 1-258 Hiromachi, Shinagawa-ku, Tokyo Sankyo Stock Company

Claims (2)

[Claims] 1. An aerial mycelium of grayish white to bright olive ash to pale yellowish orange is settled on a basal mycelium of pale yellowish orange to pale brown to bright olive ash, and spore chains are straight to curved. -Like, rarely spiral, smooth surface of spores, and grows well even on control medium containing no carbon source of Pridham Gottlieb,
A new strain of Streptomyces carbophilus that has hydroxylation ability as its ability. 2. The novel strain according to claim 1, wherein the Streptomyces carbophilus is Streptomyces carbophilus SANK 62585 (Mikokukenjoyori No. 1145).