JPS6043394A - Preparation of antibiotic oa-6129b2 - Google Patents

Abstract

PURPOSE:To prepare antibiotic OA-6129B2 selectively by fermentation, by using a specific bacterium belonging to the genus Streptomyces. CONSTITUTION:Streptomyces sp.-OA-6129 is varied [ultraviolet-light irradiation, irradiation, treated with chemical variation inducer (e.g., N-methyl-N'-nitro-nitrosoguanidine)] to give Streptomyces sp.-OA-6129-3N-504 (FERM-P 334), and it is used. Namely, the spore or hypha of the bacterium is inoculated to a nutrient source-containing medium, and cultivated aerobically at about 20-40 deg.C at about 4-9pH for about 30-90hr (preferably cultrure in a solution with aerated stirring). A mold is removed from the culture solution, and antibiotic OA-6129B2 shown by the formula is collected from the filtrate, the supernatant liquid, extracted solution, etc. by conventional procedure.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a new method for producing antibiotic OA 6129B20, and more particularly to a method for selectively producing antibiotic OA-6129B represented by the following formula % by fermentation method.

The present inventors previously developed a series of novel antibiotics represented by the following formula 11 C1iz NHCCHOH It has been shown that the substance is produced by fermentation of St. 1/Butomyces sp. 0A-6129 (Feikokenjoyori No. 11), and which antibiotics 0A-6129A (R=H), 0A- ('; 12
91'3. (Tj = 00.5.6-cis body), O
A-6129B2 (R=OH, 5,6-trans body) and (IA-6129C (R=ISO, El) were proposed.
l Meibei II 1. ! 4' No. 48,999A1, JP-A-57-62280, JP-A-57-70890, JP-A-57-95987).

The above production strain is an antibiotic nA-6129AXC)A-
6129B+ and 0A-6129B2 are also raw? However, there is a tendency to produce the antibiotic 0A-6129C. However, when converting the compound of formula (II) into other useful antibiotics, R=nso3
Compounds of formula (Il) when r1, ull et al.
2 (11 supplements, [-11 antibiotics) /
i0A-6129B,'! 0A-fi129B, it seems that the usage range of -M is larger.

That's where the real bashers come! d, l/ as substance 0A-1'i129
Capable of selectively producing Bm and/or 0A-f'1129R2: 1 strain λJ'J''r
Itokoka, who conducted +r research, ] 2 Streptomycetes
yces sp, OA, -6129) was mutated and t
A: Streptominus sp. 0A-6129
-3N -504 (Streptomycessp, 0
A-6129-3N-504) selectively produces the biological material OA 6129Bt shown by the above formula (1) lr
This led to the completion of the present invention.

1. According to the present invention, Streptomyces sp. 0A-6129-3N-504 was cultured in a nutrient medium, and from the culture, an antibiotic OA represented by the following formula % [) was obtained. 6129] 3z is provided.

The strain used in the method of the present invention, Streptomyces sp. 0A-6129-3N-504, is a new strain that has not been described in any conventional literature, and its mycological properties are as follows.

1) Morphology Under the microscope, the hyphae were found to be straight to curved (
Straight-f 1exious)'s aerial hyphae are elongated, and whorled branches are not observed. Mature [7] A spore chain consists of 10 or more oval to cylindrical spores, and no spore glue is observed. Spore size is 0.6-1.0
The surface of the spores is smooth, with a diameter of approximately 0.7 to 2.5 microns. No flagellar spores were observed 3.2) Growth conditions in various media Cultivation was carried out at 28° to 30°C unless otherwise specified.
- Also in color; jll'J's description is H. D. Tresner and E. G. Bacus (H,]') as kings, Tr.
esnerand 1i:, J, 1laclq1s
) Author, Jar-)-L, t7'・7 Pride Mitsu 11 Biology (Jr+urnal of Appl
ied MicronbinlogY) Volume 11, No. 4,
(1963), pp. 335-338, and the codes in brackets [CHMff-code] are from the Color Harmony Manual of Container Corporation of America.
Color of ral ion of America
Harmny Manual) was used.

(]) Sucrose/nitrate agar medium: Suitsuit [2(I
C:)~bright gray-yellow brown C3ge] Aerial mycelia of suit [2 (IC') ~ gray-yellow pink [5dC] were grown on medium IW growth of C3ge], and the soluble DIF pigment was mitomera tr no. r
stomach.

(21ri tv fucose asparagine jQ large medium: light yellow [2 dbl ~ bright olive base [2 ge] with good growth, bright gray [d]',! (+4 threads in the layer. It becomes grayish-yellow-pink [5dC] when separated. No soluble pigment is observed.

(3) Glycerin/asparagine agar 17fill
(ISP Medium-5): Gentle yellow pink [4gc:] ~ Bright brown [4ie]
On the good growth of light gray [d] to light gray reddish brown [5
fe] aerial mycelium. Melting 1'i: t'f=element is not recognized.

(4) Starch inorganic salt agar medium + h (r sp medium - 4): light yellow [2dh] - gray [2fe] with good growth and bright gray [d] aerial mycelia growing on it 1; No soluble dyes are produced.

(5) Tyrosine agar medium (SP medium-7): gray yellow [3
ec] ~ Light brown [4ie] growth - Hi, light gray [
d]~Aerial mycelia of light brown ash [3fe] are grown. The medium turns brownish in color.

(6) Nutrient agar medium: Good growth of light yellow [2db: or bright yellow [2fb:] to bright olive base [2ge] - Aerial mycelia of bright gray reddish brown [5fe] are attached to the husks. There are no soluble pigments.

(7) Yeast extract/malt extract agar medium (IsP
Medium-2): On the good growth of gentle yellow pink [4 gc] to bright brown [4 ie], aerial mycelia of gray yellow pink [5 dc] or slightly later bright gray [d] are attached. Soluble dyes are not occupied.

(8) Oatmeal agar medium (ISP medium-3): Good growth of gray-yellow [3ec'l ~ bright orange-yellow [3ea:l], or bright gray-yellow brown [3ge], and bright brown-gray [3fe] ~ Aerial mycelium of bright gray-reddish brown [5fe] grows 1
/, the culture medium around the lock colony is slightly brown.

(9) Malate-lime agar medium: Dark to yellow gray (2 dcl) medium IW growth with light gray [d] to light gray reddish brown [5fe] aerial mycelia growing on it, and soluble pigment vj mitomera. Growth: A dissolution zone of calcium salts is produced around the N settlement.

(10) Gelcose/peptone/gelatin medium (20℃
Culture) Pale yellow [2 dbl ~ brown with good growth and white [b] ~
Grows gray-yellow-pink [5 cb] aerial mycelia. Long-term culture (
(more than about 3 weeks) produced a brown soluble dye.

3) Physiological properties (1) Growth temperature range Yeast extract/malt extract agar JlII (I S
P medium-2) at 10°, 20°, ? 5°, 30°
.

As a result of 10 experiments at temperatures of 34°, 37°, 40°, 45°, and 50°C, almost no growth occurred at 37°C. It does not grow at all above 40°C. Growth was observed at all other temperatures. The optimum growth temperature range appears to be 20-30°C.

(2) Liquefaction of gelatin: Liquefaction.

(3) Starch hydrolysis: Decompose.

(4) Coagulation and peptonization of skim milk: Although it does not coagulate,
Peptonize.

(5) Production of melanin-like pigment: No production of melanin-like pigment was observed in peptone yeast iron agar medium (IMF medium-5) and tryptone yeast extract prosthetic medium (ISP medium-11). Although it appears very slightly brown on tyrosine agar medium, there is only a trace of melanin production.

4) Assimilation of various carbon sources (using Pridham-Gotrib agar medium) (1) L-arabinose 1 (21D--4shiIJ-Pe 10 (3) D-glucose + (4) D-fructose j~ (5) ) Sucrose Suspicious (6) Inositol - (7) L-Rhamnose + (8) Raffinose - (9) D-Mannitol + Ten is assimilated, - is not assimilated.

Based on the mycological properties of J″J, 0A-6129 is a quiet strain.
It is a strain belonging to the genus Repiomyces, and the shape of the 1-air hyphae is Section RF (Section Rcct).
It was considered that the spore surface was smooth. Aerial bacteria □The color tone of the thread is the majority of culture 11
1! %, that is, in media such as oatmeal agar, glycerin/asparagine agar, starch/inorganic salt agar, etc., it is a light gray 'd' and is a strain of the Gray 5eries'. Agar, Yeast Extract/Egis Agar, and Glucose/Asparagine Agar 1t'f ground and cultivated Tendo pink [5rLc] red type (1 ed 5eries)
f may occur. In addition, the color of the basal hyphae is amber to tendo in the medium at the initial stage of culture, and as the culture continues, it becomes yellowish to grayish brown or brown in color. Melanin pigment is produced in pegtone, yeast extract, iron agar medium and tryptone, yeast extract, broth,
In addition, the water-soluble pigments of the plant can be grown in many media.
There wasn't. However, a slight brown pigment was observed in the tyrosine agar medium, crucose peptone gelatin medium, and oatmeal agar medium.

The present inventors have identified this strain as Streptomyces sp.
-f5129-3N -504rStrepto-13
- myces sp, 0A-6129-3N-504), and was deposited with the Institute of Microbial Technology, Agency of Industrial Science and Technology, on August 5, 1983, as an international deposit under the Butapest Treaty on the Deposit of Microorganisms for the Purposes of Patent Procedures. gg334 (
FpRM BP-334) and 1. I made a contribution.

This strain is used in the aforementioned European patents (・□, (α) and is described in published specifications and published publications and is known as
It can be created by mutation treatment of SUHI-0A-6129. The mutation processing method will be explained in more detail below.

Streptomyces sp. r) A-61
By treating 29 with conventional mutation induction methods such as ultraviolet irradiation, radiation irradiation, and treatment with chemical mutagenic agents, the biosynthesis system of antibiotic 0A-6129C is deleted, and antibiotic 0A-6129Bt is transformed into "N-selection". It is possible to obtain a strain of vine that can produce this 14-chemical mutation agent. I will explain the details of the case where mutation is carried out by 1111 below in A11ll, but it is also possible to induce the mutation of the song!E (7).

fil': 4 birds: l^6X Lil'ri yeast extract/malt extract agar medium (SP medium-2
) Cultured for 2 weeks at 28°C 1-Also Streptomyces
Spores scraped from the surface of one slant culture of S.P.A-6129 were suspended in 9 mg of 0.01M phosphorus (Isona I, Lium, LiinM) at pH 7.5, and filtered through a glass filter (Manufacturer 2). In the furnace part (8, this furnace liquid 1.rr
Before diluting 9 ml of H14:/(H')j buffer to tl, add NTG to a final iQ degree of 111 (1
0 μ,! 9/me P+': Add as much as 28
℃ for 1 hour (1 hour. When the temperature is 90%, the spore effect is M!
-, 5i Atsu, IζON T G place 1 Kogawa Ruko liquid?
, 5 (centrifuged at 10X 9 for 20 min to eliminate spores)
．． Suspend in 85% physiological saline, dilute appropriately, and apply the spore suspension before dilution on IMF medium-2 [Culture at 7.28°C for 2 to 3 weeks to form colonies'; (2) Cultivation of mutant strains - As described in F, discard the colonies formed on ISP medium 2 and transfer to ISP medium 1+1-2 slope, 111 to VC L2.
Culture was performed at 8°C for 2 weeks. From the trunk culture medium of each of these strains, 1 platinum was added to 5E-4 seed medium [beef extract (], 3
%, bactodributone 0.5%, glucose 0.1
In charge, soluble sesame [starch 2.4%, acid 1n extract 05%,
Calcium carbonate 0.4%, soybean flour (TT, 1: Nomoto Co., Ltd. Meat Special etc.) 0.5%, r) H7, (1] 3
Inoculated into a test MW medium containing tri and cultured with shaking at 28°C for 2 days.

Ta. Next, add 5 ml of this culture solution Q to 1.1 cups of G.
1k (4.5 parts soybean flour, 10 parts glycerin, K2FI
P O40, 2nd section, Mg5O, 7 H2O0,1%
, CaCO30,3%, CnC125r/ml, T
) H7,0) In a 250 Inl Erlenmeyer flask containing 10 wIl for 1 year, on a rotary shaker at 28°C for 41 h. Ta.

This 1〆riji-1-Clearness 5 /L/Silica gel 601
Spot 12 on j' 254 (Merck r1:), dried for about 10 minutes in a shell desiccator, and then chloroform: methanol: 8 = 1/100 syri Tsuru Jz i'
Liquid iii (I) If 7.5) = 8: 6: 1
(7) lflilGuf deaf'-rllfl open + &, i
<tr! Ie, -c x:: IA k removal 1, Tanora Ehrlich assay 1 and Nihita L, 5<+ at 105°C
Heating for 1. As a result, the spot of antibiotic 0A-6129C disappeared j-2, and a different strain 1A1 was isolated that showed a spot of antibiotic 0A-6129B2. l(.

However, those skilled in the art will be able to search for a single-sucking creature that is suitable for the purpose of the present invention.

-1 according to the method of the invention, I7N, raw 11411 quality 0
A-(i129B2, the above bacterial strain St.
° [Subi () Aji 129-3N 504 jM!
17 - Production is carried out by inoculating the mycelia of Aspergillus into a nutrient-containing medium and aerobically increasing the flame.

As the nutrient source, those commonly used in actinomycetes, such as carbohydrates, mineral salts, and other assimilable nutrient sources, can be used. For example, glucose, glycerin, Carbon sources such as carbohydrates such as maltose, sucrose, molasses, dextrin, starch, oils and fats such as large grain oil, peanut oil, and lard;
Peptone, meat extract, soybean flour, cottonseed flour, dried yeast, corn stew liquor, yeast extract, skim milk, casei/, sodium nitrate, ammonium nitrate, ammonium sulfate, etc.; phosphorous dipotassium, salt, calcium carbonate,
Inorganic salts such as 4.M 19 magnesium can be used, and if necessary, trace amounts of metals such as cobalt and manganese can be added. Other nutrients that do not inhibit the production of antibiotic 0A-6129Bt may also be used.
8-, IzuJl, and any known nutrient source can be used. In addition, to suppress foaming during heat sterilization and culturing, silicone,
You can also add an anti-foaming agent with +ful oil.

There are particular restrictions on the blending ratio of the nutrients mentioned above.
The composition and proportion of the nutrient source suitable for the strain used can be easily determined by a person skilled in the art by simple small-scale experiments, which can vary over a range of 'M: <, E.

Additionally, the nutrient medium can be sterilized prior to culturing, and before and after sterilization, the pH of the medium is adjusted to a range of 4-9, 4I
It is advantageous to adjust r K p Fl in the range from 6 to B.

In principle, the cultivation of Streptomyces sp. 0A-61241-3N-504 in such l', H culture medium
In the production of antibiotics for general actinomycetes, it is usually used in the production of antibiotics.

It is usually preferable to culture under aerobic conditions, usually without stirring and/or with aeration. 'Also, the culture method and 17 stationary culture,
Although shaking culture and submerged culture with aeration and agitation can also be used, submerged culture is advantageous.

The vine culture temperature used was strain r)A-6124')-3N.
- The growth of 504 is qualitatively 1' No damage to the eyes and 0 antibiotics.
The force is not particularly limited as long as it can produce A-fi129B2; generally, 1 PIf within the range of 20 to 40°C, preferably 25 to 35°C is suitable.

In addition, in order to carry out the culture suitably, the pH of the culture can be adjusted to a range of 4 to 9.11' or 6 to 8 during the culture, if necessary.

In the case of large-scale mass culture, it is best to carry out a seed mother culture, inoculate this into nutrient 'j's [11], and perform liquid culture.

Cultivation can generally be continued until a sufficient amount of antibiotic 0A-6129Ba has accumulated. The culture time varies depending on the composition of the medium, culture temperature, production strain used, etc., but is usually in the range of 30 to 90 hours.

The amount of antibiotic 0A-6129By accumulated during culture can be determined by thin layer chromatography using silica gel as described above, and thereby the optimum amount of antibiotic 0A-6129By accumulated can be easily determined.

Thus, antibiotic 0A-612 accumulated in the culture.
Since 9B is water-soluble and mainly exists outside the bacterial cells, it is advantageous to remove the bacterial cells after culturing by a separation method known per se, such as filtration, centrifugation, or extraction, and to prepare the 1F5 solution. Collect from supernatant liquid, extract liquid, etc.

Recovery can be carried out by various methods known per se, in particular J.
The method using i k is advantageously applied. (>1+, for example, solvent extraction with ethyl acetate, n-butanol, etc. at low pHK and its transfer from the dissolved W layer to the Ii''TipH* layer; activated carbon, Amberlite XA, n (manufactured by Rohm and Haas) ), adsorption with Diaion IN'-20 (manufactured by Ryo Kasei Co., Ltd.), elution with methanol 7I (, acetone water, etc.); DOWEX 1×2 (manufactured by Dow Chemical Company), QAE-Sephadex A-25 ( Pharmacia M), DEAE-Cellulose Whatmanr) E-32r
Whatman), 11 E A E-Adsorption and elution with ion exchange resins such as Sephadex A-25 (Pharmacia); Sephadex G-10 (Pharmacia), Bio-Gel P-2 (Bio-Gel P-2)・Rudd 1),
Gel spasms due to cellulose, Abir SFC American Viscose Company 1! )'D column chromatography-2
2 = Graphy; Forced precipitation method by adding a solvent such as acetone;
Freeze-drying method, etc. alone or in appropriate combination,
Furthermore, it may be used repeatedly depending on the case.

Round 11. Antibiotics 0A-612QB during Nisei 9/S process
.

The behavior of
fi129Bt will be installed.

According to the method of the present invention, depending on the culture conditions, a small amount of antibiotic 0A-6129A may be produced in the culture.
29C is not produced at all, and 1): Biological material OA 6129Bt is selectively produced.

Since fMOA, -61,29By, of this biological material, is generally more stable in its salt form than in its free form, it can be used for medicinal purposes as described below, or when converted into a diluent with +A. When used as an intermediate, or when subjected to the 81S production process described above, etc.
It is preferable to process in the form of ll.

Antibiotic 0A-6129'B, (1) Conversion into its first revised form, according to methods known to it,
By treating OA-6129B2 with an inorganic or organic base, line 7! i:1'1 is possible. As an inorganic or organic base that can be used in this salt-forming reaction, i;
;11*llf, sodium hydroxide, water Y゛1　potassium, water r・1? Alkali gold hydroxides such as lithium; alkaline earth metal hydroxides such as norsium hydroxide and magnesium hydroxide; monoethylamine, dimamine, trinothylamine, monotamine, jetanol Examples include primary, secondary, or tertiary organic amines such as amines, benzathine, and fluorocaine.

Antibiotic OA-Cat 129 produced by the method of the present invention
132 is the previous 11 (Europe! 11 patent application publication Q
il, 1jll 4J-) to d[shi11 evening tail J,'') K r fan (81(') t/L picture 4 (
In addition to being considered for use as an antibacterial agent, it is also a synthetic intermediate for leading to a useful Jic antibiotic q57 substance. Other uses are also possible.

Next, the present invention will be briefly explained using Example 11.The analysis of the anti-1'y active substance used in the following examples will be carried out using a well-known antibiotic comb, Using the quality as an index, the above-mentioned twilight chromatography was performed.

Example [:A] 511 ('is/g 4'! It n1 of the following composition of 10 n Inl in an Erlenmeyer flask
Add medium C3l)-4) and add r;i,1?1 in the usual manner.
℃f15 min kill + M L7'(.

On the other hand, Streftmyces sp. OA-6129 (
F:5rep+nm)IceS81), +1 A-
6124) ”)(1?]l;R,M f(P-11)
Mutant strain 3N-!i 04 strain (FER,
4 R1) -33/l is filled with spores = 25 = minutes, and this 1 platinum is 11 nipa [shi, group 1: t
Add 101) tIl to the seed medium 101) and add 101) tIl to the bottom 11 fertilizer [18:00] in 1110-Tally Seaker (9011 rpm, amplitude 7an). ]・“p medium (Gλ'l-3) 5.O
t″4-person J also 1o/-+7+,-]nya fermenter, and with sweat 9 oxygen h1, the dissolved oxygen concentration (% saturation) in the culture solution should not be lower than 10-11. The rotation speed was controlled and the rotation rate was +5 z,/min%.The aeration and stirring culture was carried out at a temperature of 28°C for 90 hours. Silicon T (M-75 (manufactured by Shin-Etsu Chemical 6)) was used as an antifoaming agent at 0 to 1 CI.
6 was used. Culture solution ζ/sampling 17 over time, centrifuged -1- clear solution antibiotic OA -612
Coulometric measurements of the nine compounds were carried out using the thin LF Chromato Zl Roughy described above. Table 11 shows the analysis utilization at each culture time.

26- (w/v) Glucose 0.1% Soluble starch 24% Beef extract 0.3% Mi'-) Ri, 594 Bacterium-Tryptone 0.5% (:aC(')1 0.2% Tap water 97 - Composition of production medium (GM 3): Glycerin 8.0% Soy flour 3.0% Taiwanese yeast 1.n% VfgsO, 0.2%, HPO 40.2% CaCO 50.3% COCl! 5119/ml [ B] Tap water was added to 4.5 t of the fermentation solution after 90 hours of culture as described in [A] above to make 6.0 LL, and after adding Dobuco Barite A34 (Tokai Perlite Co., Ltd.), Separate the solids with Nutsche and add 4.Ot of furnace liquid (1)
I got it. Next, dissolve the solid substance in tap water again and add 4. Ot
2. An O4 p solution (I) was obtained. Combine furnace liquids (1) and (1), and use Diamond Ion FTP.
A glass column filled with 400 ml of 20 resin (4
400me/
The patient was made to inhale at a rate of hr. 40 (after washing the column with 1 ml of distilled water, 5q6 (v/v), 10 parts (v
/v) and 15% (v/v) acetone water while increasing the acetone concentration stepwise.

One section was designated as J5wl, and the eluate was fractionated and analyzed by thin layer chromatography to obtain 0A-612913! 430 txl
I got it. 0 produced in small quantities along with OA 6129B2
A-6129AJ: Contained from 1 stroke 4) 59 to both 66.

Next, the nA-6129B and fractions were pre-equilibrated with 0.01M phosphate buffer (pH 8, (l).
'Column packed with A306S (17,5tnta
25 Q ram 'I adsorbed to
Wash thoroughly with t of distilled water.1. Afterwards, the salt concentration will go from 0 to 4.
Total saline solution that varies linearly up to 1. It eluted at o and c. 129- fraction was set as 51. Each fraction was analyzed by thin layer chromatography, and fractions 33 to 55 containing OA 6129Bz were collected to obtain 130 at. This fraction was added to a Diaion HP20 column (15.0D) equilibrated in advance with 1.01M phosphate buffer (pH 8.0).
IIIX 430 City), and the eluate was eluted with a total of 600 ml of acetone water whose acetone concentration varied linearly from 0 to 20. The eluate was fractionated into 5 ml portions. Each fraction was analyzed by thin layer chromatography, and both fractions 41 to 61 containing 0A-6129B2 were collected to obtain 20 n mt. This was freeze-dried according to a conventional method to obtain a pale yellow powder of 180 ml.

The purity of this powder was 51% by thin layer chromatography.

[C] After dissolving 150 to 150 of the lyophilized product obtained in [B] above in about 101 distilled water, Q, A'E Sephadex A25 resin equilibrated with 30-001M phosphate buffer in advance Column (10j excitation x 900 city)
was adsorbed to. After washing with about 10 Q v+l of distilled water, the solution was eluted with a total of 600 ml of saline solution in which the concentration of Najinomachi changes linearly from 0 to 2%. The eluate was fractionated. Both fractions were analyzed by thin layer chromatography to obtain 100 ml of 0A-6129B2 fractions from fraction 37 to fraction 47. , n IM phosphate buffer (pT (8, (l)) was adsorbed onto a Diaion CHP20 column (10 mm Acetone water that changes linearly up to 10 cm,
A total of 8110 ml was eluted.

Each section was divided into 5 ml fractions L, and the eluate was fractionated.

Both fractions were analyzed by thin layer chromatography, and a total of 180
i+7'f, obtained. This was freeze-dried to obtain a pale yellow powder of No. 39. This powder was tested according to bionartography and the following NMRXUV, IR measurements, antibiotic 0A
-6129B2 was confirmed. The purity of this substance determined from the UV absorbance was approximately 98%.

NMR spectrum (solvent: D20, internal standard DSS) δ
・ppm' 2.45 (2H, t, J"6.5H2, NHCH□
CH2-C0), 2.75-3.60 (IIH, m,
C-4H2,4-6F].

3.94 (I HX s, lo-0H-Co), H 3,95-4,35 (211, m, C-5Fl, C
B, -CI-).

UV absorption spectrum 0.01M phosphate buffer (pH 8,4) ax nm(t)=3no(54('10) KBr -1+.

TR absorption spectrum νmaxc′rn ・1760
(β-lactam) 1 (560 (amide) 1600 (galboxylate) 33- - Notificationq

Claims (1)

[Claims] Streptomyces sp□A-6129-3N-5
04 in a nutrient medium, and the antibiotic OA 6129By represented by the following formula % (%) is collected from the culture.