JPH08239385A - Fo-1289 substance and its production - Google Patents

Abstract

PURPOSE: To obtain a new substance useful for preventing and treating diseases caused by accumulation of cholesterol, having inhibitory activity against acyl coenzyme A cholesterol acyltransferase, by culturing a specific fungus belonging to the genus Aspergillus. CONSTITUTION: This new substance FO-1289 substance is shown by the formula (R1 to R4 are each H or an acyloxy), has inhibitory activity against acyl coenzyme A cholesterol acyltransferase and is useful for preventing and treating hyperlipemia, hypercholesterolemia, atherosclerosis, angina pectoris, cardiac infarction, etc., caused by cholesterol accumulation. The new substance is obtained by inoculating a fungus [e.g. Aspergillus sp.F0-1289 (FERM BP-4242) etc.] belonging to genus Aspergillus, capable of producing FO-1289 substance, into a medium, subjecting the fungus to shaking culture at 27 deg.C for 48 hours to give a seed culture solution, adding the culture solution to a medium in a jar fermenter, subjecting the substance to aerobic spinner culture at 27 deg.C for 120 hours to accumulate the product and collecting the product from the culture substance.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to acylcoenzyme A.
Novel substance F having cholesterol acyltransferase inhibition
O-1289 substance and its manufacturing method.

[0002]

2. Description of the Related Art Conventionally, some drugs for treating hyperlipidemia are known. As a therapeutic drug for hyperlipidemia,
(1) Cholesterol biosynthesis inhibition, (2) Cholesterol absorption inhibition, (3) Cholesterol catabolism promotion,
(4) A drug having an action of suppressing the synthesis of lipoprotein is known.

[0003]

In recent years, with the improvement of eating habits, symptoms caused by cholesterol accumulation such as hyperlipidemia and arteriosclerosis in adults have been regarded as a modern disease. Hyperlipidemia is known as one of the factors that promote the progression of arteriosclerosis, and can reduce ischemic heart disease by lowering blood cholesterol. Further, it is desired to develop a more effective and safe therapeutic drug for hyperlipidemia, particularly hypercholesterolemia, such that the incidence of myocardial infarction increases with hyperlipidemia.

Cholesterol becomes cholesterol ester by acyl group transfer from acyl coenzyme A,
It is accumulated intracellularly and in blood lipoproteins. The enzyme that catalyzes this acyl group transfer reaction is acyl coenzyme A cholesterol acyl transferase, which is deeply involved in the absorption of cholesterol from the intestinal tract and the formation of foam cells in the coronary arteries.

Therefore, it is speculated that a substance that inhibits acylcoenzyme A cholesterol acyltransferase is effective for such diseases. In such a situation,
Providing a substance having an acylcoenzyme A cholesterol acyltransferase inhibitory activity is useful for treating adult diseases such as hyperlipidemia and arteriosclerosis based on it.

[0006]

As a result of continuing research on metabolites produced by microorganisms, the present inventors have found that acylcoenzyme A cholesterol acyltransferase in cultures of FO-1289 strain isolated from fresh soil. It was found that a substance having inhibitory activity was produced. Then, an acylcoenzyme A cholesterol acyltransferase inhibitory active substance was separated from the culture and purified to obtain each substance having the physicochemical properties described below. Since these substances have not been known at all in the past, this substance is FO-1289.
I decided to call it a substance.

The present invention has been completed based on the above findings.
And the molecular formula C₂₇H₃₃NO_FiveFO-1 represented by
289E substance, molecular formula C₂₈H₃₅NO_FiveFO- represented by
1289F substance, molecular formula C₂₇H₃₃NO₆FO represented by
-1289G substance, molecular formula C ₂₈H₃₅NO₆F represented by
O-1289H substance, molecular formula C₃₄H₄₃NO_TenRepresented by
FO-1289I substance, molecular formula C₃₃H₄₁NO_TenRepresented by
FO-1289J substance, FO-1289K substance and F
O-1289L material.

Further, the present invention cultivates in a medium a microorganism belonging to the genus Aspergillus and having the ability to produce the FO-1289 substance, to produce and accumulate the FO-1289 substance in the culture, and from the culture, FO- The present invention provides a method for producing FO-1289 substance, which comprises collecting 1289 substance.

The microorganism having the ability to produce the FO-1289 substance of the present invention (hereinafter referred to as FO-1289 substance-producing bacterium) belongs to the genus Aspergillus. For example, the Aspergillus sp.
gillus sp. ) The FO-1289 strain is an example of the most effectively used strain of the present invention, and the bacteriological properties of this strain are as follows.

I. This strain is a malto extract agar medium, a Tuapek yeast extract agar medium,
It grows satisfactorily on a 20% sucrose tuapec yeast extract agar medium, and conidia also adhere well. When the colonies grown on the Tuapek yeast extract agar medium are observed under a microscope, the hyphae are transparent and have septa, and the conidia stalks mainly grow directly from the basal hyphae, and the surface is smooth.

The tip of the conidia stalk forms a bulge and a flask-shaped apex (diameter 10 to 25 μm). No meteor is formed and the fluoride grows directly on the apex. Conidia have a diameter of 2 to 3 μm, and their shapes are spherical and subspherical.

II. Various properties on culture (1) The culture findings of this strain are shown in Table 1. This finding is the result of macroscopic observation when cultured at 25 ° C. for 7 days on various media.

[0013]

[Table 1]

(2) The growth condition of Tuapec yeast extract agar medium when cultured at 37 ° C. for 7 days is very vigorous (80 mm or more). Meanwhile, 5
It did not grow when cultured at 7 ° C for 7 days. In all of the above-mentioned media, formation of secretory fluid and sclerotia associated with the growth of the fungus was not observed.

III. Physiological properties (1) Growth temperature range: 15 to 47 ° C. (2) Optimal growth temperature range: 27 to 40 ° C. (3) Growth pH range: 3 to 11 (4) Optimal growth pH range : 5-8 (5) Distinction between aerobic and anaerobic: aerobic

Based on the above-mentioned morphological characteristics, culturing characteristics and physiological characteristics of the FO-1289 strain, an attempt was made to compare it with known strains. As a result, the strain was identified as Aspergillus (Aspergillus).
gils) genus, and was named Aspergillus sp. FO-1289. This strain is Aspergillus sp.
p. ) Deposited as FO-1289 at the Institute of Biotechnology, Industrial Technology Institute, AIST. The deposit date is April 15, 1991
The day and the accession number is FERM BP-4242.

The FO-1289-producing bacterium has been described above. However, as a general property of the bacterium, the mycological properties are extremely liable to vary, and are not constant. , For example N-
It is a well-known fact that mutation is carried out by means of artificial mutagenesis such as methyl-N-nitro-N-nitrosoguanidine, ethyl methanesulfonate, etc., and as well as such artificial mutants, natural mutants and Aspergillus spp. Any strain belonging to S. cerevisiae and having the ability to produce the FO-1289 substance can be used in the present invention. In addition, strains mutated by cell engineering such as cell fusion and gene manipulation are also included as substance FO-1289 substance-producing bacteria.

In the present invention, first, a FO-1289 substance-producing bacterium belonging to the genus Aspergillus is cultured in a medium. In culturing the bacterium, a fungal culturing method is generally used. As a medium, a carbon source that microorganisms can assimilate,
A nutrient medium containing an assimilable nitrogen source and, if necessary, an inorganic acid salt or the like is used. As the assimilable carbon source, glucose, sucrose, sugar concentrate, dextrin, cellulose and the like are used alone or in combination.

As a nitrogen source which can be assimilated, organic nitrogen such as peptone, meat extract, yeast extract, dry yeast, soybean powder, corn steep liquor, cottonseed meal, casein, soybean protein hydrolyzate, amino acid and urea. Sources, inorganic nitrogen compounds such as nitrates, ammonium salts and the like may be used alone or in combination. In addition, inorganic salts such as sodium salt, potassium salt, calcium salt, magnesium salt, and phosphate, and heavy metal salts are added as necessary. Further, if necessary, a micronutrient, a growth promoting substance, a precursor substance or the like which promotes the growth of the bacterium or the production of the FO-1289 substance may be appropriately added to the medium.

Culturing is usually carried out under aerobic conditions such as shaking or aeration stirring culture. From the industrial point of view, deep aeration stirring culture is preferred. It is preferable to carry out the culture at a pH of about neutral. The culture temperature may be 20 to 37 ° C.,
It is usually good to keep at 24 to 30 ° C. Culture time is usually 2
Since the FO-1289 substance of the present invention is accumulated by culturing for about 3 days, the culturing may be terminated when the accumulated amount in the culture reaches the maximum.

The culture conditions such as the medium composition, the liquidity of the medium, the culture temperature, the stirring speed, and the aeration rate are appropriately adjusted and selected so as to obtain preferable results depending on the kind of the strain to be used and the external conditions. It goes without saying that it will be done. In liquid culture, when foaming occurs, a defoaming agent such as silicone oil, vegetable oil, or surfactant can be used as appropriate. The FO-1289 substance accumulated in the culture thus obtained is contained in the cells and the culture filtrate, and thus the culture is centrifuged to separate the culture filtrate and the cells, and It is advantageous to collect the FO-1289 material.

To collect the FO-1289 substance from the above-mentioned culture filtrate, first, the culture filtrate is extracted with a non-hydrophilic organic solvent such as ethyl acetate, butyl acetate or benzene, and the extract is concentrated under reduced pressure to obtain crude FO. -1289 substance is obtained.
This crude substance is further subjected to a known method usually used for purification of a fat-soluble substance, for example, column chromatography using a carrier such as silica gel or alumina to obtain FO-1.
289 substances can be separated and purified.

In order to collect the FO-1289 substance from the cells, the cells are extracted with a water-containing hydrophilic organic solvent such as water-containing acetone or water-containing methanol, and the obtained extract is concentrated under reduced pressure. The concentrate is extracted with a non-hydrophilic organic solvent such as ethyl acetate, butyl acetate or benzene, and the obtained extract is separated and purified by combining with the extract obtained from the above culture filtrate, or by the same method as described above. FO-1289
The substance can be separated and purified.

Next, the physicochemical properties of the FO-1289 substance of the present invention will be described. FO-1289 according to the invention
E substance, FO-1289F substance, FO-1289G substance, FO-1289H substance, FO-1289I substance, F
O-1289J substance, FO-1289K substance and FO-
The physicochemical properties of the 1289L substance are as shown in Tables 2 and 3.

[0025]

[Table 2]

[0026]

[Table 3]

Solubility in solvent: Soluble in methanol, ethanol, acetonitrile, ethyl acetate, benzene,
Insoluble in water Basic, acidic, neutral: Neutral substance properties: yellow powder Chemical structure:

FO-1289E substance R ₁ ; H, R ₂ ; H, R ₃ ; -O-CO-CH ₃ ,
R _4; -H FO-1289F substance _{R 1; H, R 2;} H, R 3; -CO-CH 2 -CH 3,
R ₄ ; -H

FO-1289G substance R ₁ ; H, R ₂ ; H, R ₃ ; --CO--CH ₃ , R ₄ ;
OH FO-1289H substance R ₁ ; H, R ₂ ; H, R ₃ ; -CO-CH ₂ -CH ₂ ,
R ₄ ; -OH

FO-1289I substance R ₁ ; --CO--CH ₂ --CH ₃ , R ₂ ; --CO--CH _{2
-CH 3, R 3; -CO-} CH 2 -CH 3, R 4; -O
HFO-1289J substance R ₁ ; -CO-CH ₃ , R ₂ ; -CO-CH ₂ -C
_{H 3, R 3; -CO-} CH 2 -CH 3, R 4; -OH

FO-1289K substance R ₁ ; --CO--CH ₂ --CH ₃ , R ₂ ; --CO--C
_{H 3, R 3; -CO-} CH 2 -CH 3, R 4; -OH FO-1289L substance _{R 1; -CO-CH 2 -CH} 3, R 2; -CO-CH 2
_{-CH 3, R 3; -CO-} CH 3, R 4; -OH

Next, the biological properties of the FO-1289 substance of the present invention will be described. (1) Inhibitory effect on rat-derived acyl coenzyme A cholesterol acyltransferase The effect on acylcoenzyme A cholesterol acyltransferase activity is as described by Kyoda et al. (The Journal of Antibiotics, 44, 136, 199).
1 year), using a crude enzyme prepared from rat liver microsome fraction, 100 mM phosphate buffer (pH 7.4)
Medium 300μM bovine serum albumin, 30μM [1- ¹⁴ C]
Oleoyl-CoA (0.02 μCi), 30 μM Cholesterol (1/30 weight of Triton WR-1339).
(Dissolved in step 3) was added to make a total volume of 200 μl.
After reacting at 7 ° C. for 30 minutes, total lipids were extracted with a mixture of chloroform: methanol (2: 1), and then extracted with TLC (Kieselgel GF ₂₅₄ , petroleum ether: diethyl ether: acetic acid = 90: 10: 1 as a developing solvent). After separating the lipids, the radioactivity incorporated in the cholesterol ester fraction was measured by R
It was analyzed with an I scanner (manufactured by Ambis) to measure the acylcoenzyme A cholesterol acyltransferase activity. The results of calculating the concentration that inhibits the activity of this enzyme by 50% are shown in Tables 4 and 5.

[0033]

[Table 4]

[0034]

[Table 5]

[0035]

As described above, FO-1289 of the present invention.
Since the substance exhibits a remarkable inhibitory activity against acylcoenzyme A cholesterol acyltransferase, it is useful for the prevention and treatment of diseases caused by human cholesterol accumulation.

[0036]

EXAMPLES Next, the present invention will be specifically described with reference to examples, but the present invention is by no means limited thereto. Glucose 2.0 in a 500 ml Erlenmeyer flask
%, Polypeptone 0.5%, yeast extract 0.2%, magnesium sulfate 0.05%, potassium dihydrogen phosphate 0.1%, agar 0.1% (pH (pH))
(Adjusted to 6.0) 100 ml was charged, cotton plugged, steam sterilized, and grown on an agar medium, Aspergillus sp. FO-1289.
(FERM BP-4242) was aseptically inoculated with a platinum loop and shake-cultured at 27 ° C. for 48 hours to obtain a seed culture solution.

Further, 20 l of the same medium as above was charged into one 30 l jar fermenter, and 200 ml of the above seed culture was aseptically transplanted after cooling with steam sterilization, and the stirring speed was 250 r.
Under culturing conditions of pm and an aeration rate of 10 L / min, aeration and stirring culture was carried out at 27 ° C. for 48 hours to obtain a sufficient amount of seed culture solution.

On the other hand, soluble starch 3.0%, glycerol 1.0%, kinako 2.0%, dry yeast 0.3%, KCl 0.3 per 1 unit of 400 L jar fermenter.
_{%, KH 2 PO 4 0.05%} , MgSO 4 · 7H 2 O
Seed culture medium 2L prepared by charging 0.05%, CaCO ₃ 0.2%, nicotinic acid (Merck) 0.002% (adjusted to pH 6.5), steam sterilization cooling, and culturing with the above 30L jar fermenter. Aseptically transplanted, stirring speed 250r
The culture was performed with aeration and stirring at 27 ° C. for 120 hours under the conditions of pm and an aeration rate of 10 L / min.

After culturing, 200 L of the culture solution was added to ethyl acetate 18
Extraction was performed with 0 L, and the extract was concentrated under reduced pressure to obtain a structured product. Silica gel (400 g, manufactured by Merck & Co., Ar
t. 9385) column and charged with chloroform-
Column chromatography was performed eluting with methanol (99: 1). Each fraction was fractionated into 200 ml fractions, and the fractions containing active ingredients were collected and dried under reduced pressure to give 18.0 g of crude active substance.

This is dissolved in a small amount of acetonitrile water,
ODS gel (Sen filled with 55% acetonitrile water)
shu Sci. Co. , ODS-SS-1020T)
A 200 g column was charged and column chromatography was performed. Fraction each 50ml,
Fractions containing active ingredients were collected and dried under reduced pressure to obtain 800 mg of crude substance I and 320 mg of crude substance II. Then, the crude substance I was subjected to high performance liquid chromatography (S
enshu Sci. Co. , ODS-H-6251,
30 × 250 mm, flow rate 20.0 ml / min, detection, UV
320 nm, elution solvent 52.5% acetonitrile water) was used for fractionation.

Next, elution time is 47.0 minutes, 52.5
Min, 37.5 min, 32.0 min, 32.5 min, the fractions eluted respectively were collected, the organic solvent was removed, and the aqueous layer was extracted with ethyl acetate layer to give FO-1289G substance at 17.0 m.
g, FO-1289I substance 12.8 mg, FO-12
89J substance 86.4 mg, FO-1289K substance 5
8.0 mg and 65.4 mg of FO-1289L substance were obtained respectively.

Next, the crude substance II was subjected to high performance liquid chromatography (Senshu Sci. Co., ODS-H-6).
251, 30 × 250 mm, flow rate 20.0 ml / min, detection, UV320 nm, elution solvent 60% acetone nitrile water) and fractionated. Elution time 30.0 minutes, 47.0
Fractions eluting at 32.0 minutes were collected, the organic solvent was removed, and the aqueous layer was extracted with an ethyl acetate layer to form FO-
71.4 mg of 1289E substance, 35.8 mg of FO-1289F substance and 5.0 mg of FO-1289H substance.
Each isolated.

[Brief description of drawings]

FIG. 1 is an ultraviolet absorption spectrum of a FO-1289E substance.

FIG. 2 is an infrared absorption spectrum of the FO-1289E substance.

FIG. 3 is a ¹ H NMR spectrum of FO-1289E substance.

FIG. 4 is a ¹³ C NMR spectrum of FO-1289E substance.

FIG. 5 is an ultraviolet absorption spectrum of a FO-1289F substance.

FIG. 6 is an infrared absorption spectrum of a FO-1289F substance.

FIG. 7 is a ¹ H NMR spectrum of FO-1289F substance.

FIG. 8 is a ¹³ C NMR spectrum of FO-1289F substance.

FIG. 9 is an ultraviolet absorption spectrum of a FO-1289G substance.

FIG. 10 is an infrared absorption spectrum of a FO-1289G substance.

FIG. 11 is a ¹ H NMR spectrum of FO-1289G substance.

FIG. 12 is a ¹³ C NMR spectrum of FO-1289G substance.

FIG. 13 is an ultraviolet absorption spectrum of a FO-1289H substance.

FIG. 14 is an infrared absorption spectrum of a FO-1289H substance.

FIG. 15 is a ¹ H NMR spectrum of a FO-1289H substance.

FIG. 16 is a ¹³ C NMR spectrum of FO-1289H substance.

FIG. 17 is an ultraviolet absorption spectrum of a FO-1289I substance.

FIG. 18 is an infrared absorption spectrum of a FO-1289I substance.

FIG. 19 is a ¹ H NMR spectrum of FO-1289I substance.

FIG. 20 is a ¹³ C NMR spectrum of FO-1289I substance.

FIG. 21 is an ultraviolet absorption spectrum of the FO-1289J substance.

FIG. 22 is an infrared absorption spectrum of the FO-1289J substance.

FIG. 23 is a ¹ H NMR spectrum of a FO-1289J substance.

FIG. 24 is a ¹³ C NMR spectrum of FO-1289J substance.

FIG. 25 is an ultraviolet absorption spectrum of a FO-1289K substance.

FIG. 26 is an infrared absorption spectrum of the FO-1289K substance.

FIG. 27 is a ¹ H NMR spectrum of FO-1289K substance.

FIG. 28 is a ¹³ C NMR spectrum of FO-1289K substance.

FIG. 29 is an ultraviolet absorption spectrum of the FO-1289L substance.

FIG. 30 is an infrared absorption spectrum of a FO-1289L substance.

FIG. 31 is a ¹ H NMR spectrum of FO-1289L substance.

FIG. 32 is a ¹³ C NMR spectrum of FO-1289L substance.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical display location C12P 17/18 C12P 17/18 D // (C07D 493/04 309: 38 311: 92) (C12N 1/14 C12R 1:66) (C12P 17/18 C12R 1:66)

Claims (27)

[Claims] 1. The following formula: (In the formula, R ₁ , R ₂ , R ₃ and R ₄ are hydrogen or an acyloxy group) A FO-1289 substance. 2. FO-128 belonging to the genus Aspergillus
Production of FO-1289 substance characterized by culturing a microorganism capable of producing 9 substances in a medium to produce and accumulate the FO-1289 substance in the culture, and collecting the FO-1289 substance from the culture. Law. 3. FO-128 belonging to the genus Aspergillus
Microorganisms capable of producing 9 substances are Aspergillus sp. FO.
The method according to claim 2, which is -1289 (FERM BP-4242). 4. FO-128 belonging to the genus Aspergillus
A microorganism capable of producing 9 substances. 5. The microorganism according to claim 4, which is Aspergillus sp. FO-1289. 6. The following formula: (In the formula, R ₁ , R ₂ and R ₄ are hydrogen and an R ₃ acetoxy group) A FO-1289E substance. 7. The following formula: (In the formula, R ₁ , R ₂ and R ₄ are hydrogen, and R ₃ is a propoxy group) FO-1289F substance. 8. FO-128 belonging to the genus Aspergillus
A microorganism having the ability to produce 9F substance is cultivated in a medium to produce and accumulate FO-1289F substance in the culture,
A method for producing a FO-1289F substance, which comprises collecting the FO-1289F substance from the culture. 9. FO-128 belonging to the genus Aspergillus
A microorganism having the ability to produce 9F substance is Aspergillus sp. FO.
It is -1289 (FERM BP-4242), The manufacturing method of Claim 8. 10. The following formula: (In the formula, R ₁ and R ₂ are hydrogen, R ₃ is an acetoxy group, R
FO-1289G substance represented by ₄ ). 11. FO-12 belonging to the genus Aspergillus
Production of FO-1289G substance, which comprises culturing a microorganism capable of producing 89G substance in a medium to produce and accumulate the FO-1289G substance in the culture, and collecting the FO-1289G substance from the culture. Law. 12. FO-12 belonging to the genus Aspergillus
A microorganism having the ability to produce 89G substance is Aspergillus sp.
The method according to claim 11, which is O-1289 (FERM BP-4242). 13. The following formula: (In the formula, R ₁ and R ₂ are hydrogen, R ₃ is a propoxy group,
FO-1289H substance represented by R ₄ is a hydroxyl group. 14. FO-12 belonging to the genus Aspergillus
Production of FO-1289H substance characterized by culturing a microorganism capable of producing 89H substance in a medium to produce and accumulate the FO-1289H substance in the culture, and collecting the FO-1289H substance from the culture. Law. 15. FO-12 belonging to the genus Aspergillus
A microorganism having the ability to produce 89H substance is Aspergillus sp.
The production method according to claim 14, which is O-1289 (FERM BP-4242). 16. The following formula: (In the formula, R ₁ , R ₂ and R ₃ are propoxy groups, and R ₄ is a hydroxyl group) FO-1289I substance. 17. FO-12 belonging to the genus Aspergillus
Production of FO-1289I substance, characterized in that a FO-1289I substance is produced and accumulated in the culture by culturing a microorganism capable of producing the 89I substance in a medium, and the FO-1289I substance is collected from the culture. Law. 18. FO-12 belonging to the genus Aspergillus
The microorganism having the ability to produce 89I substance is Aspergillus sp.
The method according to claim 17, which is O-1289 (FERM BP-4242). 19. The following formula: (In the formula, R ₁ is an acetoxy group, R ₂ and R ₃ are propoxy groups, and R ₄ is a hydroxyl group). 20. FO-12 belonging to the genus Aspergillus
Production of FO-1289J substance, which comprises culturing a microorganism having the ability to produce 89J substance in a medium to produce and accumulate the FO-1289J substance in the culture, and collecting the FO-1289J substance from the culture. Law. 21. FO-12 belonging to the genus Aspergillus
The microorganism having the ability to produce 89J substance is Aspergillus sp.
The production method according to claim 20, which is O-1289 (FERM BP-4242). 22. (In the formula, R ₁ and R ₃ are propoxy groups, R ₂ is an acetoxy group, and R ₄ is a hydroxyl group). 23. FO-12 belonging to the genus Aspergillus
Production of FO-1289K substance, which comprises culturing a microorganism having the ability to produce 89K substance in a medium to produce and accumulate the FO-1289K substance in the culture, and collecting the FO-1289K substance from the culture. Law. 24. FO-12 belonging to the genus Aspergillus
The microorganism having the ability to produce 89K substance is Aspergillus sp.
The production method according to claim 23, which is O-1289 (FERM BP-4242). 25. The following formula: (In the formula, R ₁ and R ₂ are propoxy groups, R ₃ is acetoxy group, and R ₄ is hydroxyl group) FO-1289L substance. 26. FO-12, which belongs to the genus Aspergillus
Production of FO-1289L substance, which comprises culturing a microorganism having an ability to produce 89L substance in a medium to produce and accumulate the FO-1289L substance in the culture, and collecting the FO-1289L substance from the culture. Law. 27. FO-12 belonging to the genus Aspergillus
The microorganism having the ability to produce 89L substance is Aspergillus sp.
27. The method according to claim 26, which is O-1289 (FERM BP-4242).