JPS60184391A - Antibiotic tan-585a, its preparation and novel strain belonging to flexibacter - Google Patents

Abstract

PURPOSE:To prepare novel antibiotic TAN-585A showing no toxicity to mammals, etc., having antibacterial action mainly on Gram-negative bacteria, by cultivating a specific bacterium belonging to the genus Flexibacter, collecting a product formed and accumulated in the culture. CONSTITUTION:Strain Flexibacter alginoliquefaciens YK-49 (FERM P-7484) separated from a soil specimen (collected mount YOSHINO in YOSHINO county in NARA prefecture) is used as a bacterium capable of producing antibiotic TAN- 585A. Namely, the bacterium is cultivated in a medium containing glucose, etc. a carbon source, soybean powder, urea, etc. as a nitrogen source by aerated spinner culture at about 4-8pH at about 15-35 deg.C for about 8-168hr, and antibiotic TAN-585A [analytical composition: carbon 46.2+ or -2%, hydrogen 4.9+ or -1%, nitrogen 7+ or -1%, and sodium 5.6+ or -1%, molecular weight: 750+ or -22, appearance: white powder (properties as disodium salt)] is collected from the culture fitrate by a conventional procedure.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel antibiotic TAN-585A and its salts,
Its manufacturing method and 71/Yashinoguri 7-A's 4 lido song 1
) 11 Mi 7 Fruit) 21 ■ Lee (J Umo The present inventors isolated a large number of microorganisms from soil dust for the purpose of discovering new antibiotics, and conducted a separate search for the antibiotics they produced.
The fact that a certain type of microorganism produces a new antibiotic, that the microorganism belongs to the genus Flexibacter, and that by culturing the microorganism in an appropriate medium, an antibiotic that exhibits antibacterial activity mainly against Gram-negative bacteria can be produced in a medium. After learning about the scales that accumulate in the bacteria, we isolated this antibiotic, confirmed that it was a new antibiotic from its physicochemical and biological properties, and designated it as an antibiotic TAN. -58
I decided to call it 5A. The present inventors completed the present invention as a result of further research based on these findings.

The present invention provides 1) antibiotic TAN-585A and its salts, 2) antibiotic TAN-5 belonging to the genus Flexibacter.
85A Ikuya koji is cultured in a medium, and antibiotics and gT are added to the culture.
A method for producing the antibiotic TAN-585A, which allows the production and accumulation of AN-585A and its collection, 3)
The oxidative fermentative test is a new bacterial species, Flexibacter alginoliquefaciens, which is non-degradable and has the ability to decompose attvoxic acid.

In addition, in this application, antibiotic'/(TJIJ-585A may be simply referred to as "TAN-585A".

The antibiotic TAN-585A-producing bacteria used in the present invention include Flexibacter (F'1exi-bacterium).
Any microorganism that belongs to the genus r) and has the ability to produce the antibiotic TAN-585A may be used.

An example of the antibiotic TAN-585A producing bacteria is Flexibacter alginoliquefaciens Y, which was collected by the present inventors from soil dust in Mt. Yoshino, Yoshino District, Nara Prefecture.
K-49 strain (hereinafter sometimes abbreviated as "YK-49 strain") is mentioned.

The mycological properties of the YK-49 strain are as follows.

(a) Shape Observation after 2 days of culturing on a broth agar slant at 24°C revealed that the diameter of the regular cell is 04 to 0.7 μm 9 Normal length Normally -10 μm + 7
) #TI exhibits a long rod shape, but in rare cases may exhibit a filament shape of 50 to 70 μm.

Does not have fimbriae. It has motility due to briding. It does not form spores or microcysts, is negative in Durham staining, and does not exhibit acid fasting properties.

(b) Growth status on various media The cells were cultured at 24°C and observed for 1 to 14 days.

■Juice-filled plate culture: Forms circular, convex, or golden-edged colonies. The surface is smooth, translucent, and white to cream colored. No diffusible dye is produced.

■Juice agar slant culture: Shows good spread-like growth and a glossy light brown color.

■ Meat juice liquid culture 4N: Grows in a turbid manner, produces a small amount of sedimentation, and forms a weak #i ring.

■Meat juice gelatin puncture culture: Growth is weak.

(Lidmus milk: Betatonization is positive for coagulation, white turbidity is observed at the bottom, and decolorization is observed, but acid formation and coagulation are not observed.

(0) Fabric properties ■ Nitrate reduction: Negative ■ Denitrification reaction: Negative ■ MR (Methyl Red) test: Negative ■ vP (Voges-Proskauer lv) test: Negative ■ Indole production: Negative ■ Hydrogen sulfide production: Negative ■ Hydrolysis of starch: Positive ■ Utilization of citric acid 2 Positive ■ Utilization of inorganic nitrogen sources: ) Potassium nitrate: Negative ■) Each medium): Does not produce soluble pigments.

■Urease: Negative ■Oki Vdase: Positive O Catalase: Positive 0 Range of raw stomach 1) pH: p) Grows at 14.9 to 8.5, but the pTI of the 11th harvest is 5.4 to 66° II) Temperature: Grows at 6-35℃, but the optimum temperature is 14-35℃
31℃.

■Attitude towards oxygen: aerobic ■or (oxidative fermentative) test [Hugh-Leif-8on
) method]: Production of acid and gas from non-decomposed Oa: Gas availability (Davis medium) L-arabinose ± -+ D-xylone -+ D-glucose ± -+ D -Mannose -+ D-Hookdose -+ D-Galactose - -+ Maltose -+ Di'Yo sugar -+ Lactose -+ Trehalose - Tenri-Sorvit --- D-Mannitol - −+ Inosit −−− Gly7rin −−+ Dene 1 − Decomposition of 10 polyacrylates: Does not decompose agar, cellulose, carboxymethyl cellulose, and colloidal chitin. Decomposes alginic acid.

@0% salt broth liquid culture: Grows.

Meat juice liquid Lf with 05% salt! Strong f: Does not grow.

The YK-49 strain having the following thematic properties was selected from Bergey's Manual of Determinant Bacteriology.
erminative Bacteriology)
3rd edition and International Journal of
Systematic bacteriology
ionalJournal of 8yatemati
a Bacteriology) Volume 30, 215-4
20 (1980), Vol. 32, pp. 146-149 (
(1982), it is a rod-shaped or filament-shaped Gram-negative bacterium that does not have the ability to form microcysts and exhibits motility due to briding.
Since it does not decompose either carboxymethylcellulose or colloidal μ chitin, does not require salt, and is not resistant to salt, it is appropriate to classify it as belonging to the genus Flexibacter. Therefore, when we compared the YK-49 strain with known strains of the genus Flexibacter, we found that the YK-49 strain was as follows.
The properties of the 49 strains were different from known strains in that 1) Oxidate fermentativetist was non-degradable, and 2) they had the ability to decompose alginic acid. Therefore, we recognized this strain as belonging to a new bacterial species, and identified it as Flexibacter alginoliquefaciens (Fle.
xibacter alginoliquefacie
ns).

In addition, this strain has been deposited with the Ministry of International Trade and Industry, Agency of Industrial Science and Technology, Biophobic Industrial Technology Research Institute (F'R Engineering) since February 22, 1980, with accession number FERM P-741:? Finally, from February 20, 1980, IFO14321 was sent to the Fermentation Research Institute.
Both have been deposited as .

The Flexibacter bacteria used in the present invention are generally susceptible to changes in their properties, and can be easily mutated by artificial mutagenesis means using ultraviolet rays, X-rays, chemicals (e.g., nitrosoguanidine, ethyl methanesulfonic acid), etc. Therefore, no matter what kind of mutant strain, T
Anything capable of producing AN-585 can be used in the present invention.

When culturing TAN-585A producing bacteria, carbon sources such as glucose, sorghum, maltose, blackstrap molasses,
Glycerol, fats and oils (e.g. soybean oil, olive oil, etc.)
, organic acids (eg, citric acid, succinic acid, gluconic acid, etc.) that can be assimilated by bacteria are used as appropriate. Examples of nitrogen sources include soybean flour, cotton pulp, corn steep liquor, dried yeast, yeast extract, meat extract, Beitone, urine S, ammonium WC acid, and ammonium nitrate.

Organic nitrogen compounds and front nitrogen compounds such as ammonium mide and ammonium phosphate can be used. Examples of inorganic salts include sodium chloride.

M and M salts necessary for normal cell culture such as potassium chloride, calcium ash, magnesium sulfate, potassium phosphate, and disodium phosphate are used alone or in combination with Ar1 as appropriate.

In addition, heavy metals such as sulfate @1 iron and copper sulfate, and vitamin B
+, vitamin chains such as biotin, etc. are also added as necessary. Furthermore, antifoaming agents and surfactants such as silicone oil and polyalkylene glycol ether may be added to the medium. Helps the growth of sexual bacteria, TAN-585
Organic or inorganic substances that promote the production of A may be added as appropriate.

The culturing method may be the same as a general antibiotic production method, and solid culture or liquid culture may be used. For liquid culture, use static @culture or agitation culture.

Any method such as shaking culture or oil culture may be used, but aerated agitation culture is particularly preferred. Also, the culture temperature is approximately 15℃
-35b is preferred, and the PR of the medium is in the range of about 4-8 for approximately 8 hours to 168 hours, preferably 24 hours to
Incubate for 144 hours.

Target antibiotic T Alx-585A from culture product
In order to collect the metabolites produced by microorganisms, separation means that are normally used for collecting them from cultured materials of fish organisms are appropriately used. For example, the antibiotic TAN-585A is -■
■■■■■■ has chemical properties as a water-soluble acidic substance and is mainly contained in the culture filtrate. First, a transient aid is added to the culture solution and the bacterial cells are isolated by transient or centrifugation. The culture medium P solution obtained was transferred to a suitable carrier.
Advantageously, a method is used in which the active ingredients in the furnace liquid are absorbed 7a, and then the active substances are declared with an appropriate solvent and separated and collected. Activated carbon as a chromatography carrier,
Utilizes the difference in adsorption properties of compounds such as silica gel, powdered cellulose, and adsorbent 4FJI fat.
Those that utilize differences in the functional groups of compounds, such as anion-exchanged cellulose, or those that utilize differences in molecular locations of compounds, such as molecular sieving carriers, are advantageously used. In order to elute the target compound from these carriers, the combination differs depending on the type and properties of the carrier, but for example, aqueous solutions of water-soluble organic solvents, such as aqueous acetone, aqueous alcohols, acids, alkali, etc. Buffer solutions or aqueous solutions containing inorganic or organic salts are used in appropriate combinations.

Further, the crude substance of the present antibiotic obtained by these chromatography can be subjected to preparative high performance liquid chromatography for further purification.

More specifically, anion exchange resins such as DOWEX-1 (manufactured by Dow & Chemical Co., USA), Amberlite IRA-68,400,
402,410 (manufactured by Rohm and Haas, USA)
, Diaion 5A-21A and C (Mitsubishi Kasei Corporation,
(Japan) etc., the antibiotic in the filtrate is adsorbed,
It can be eluted with aqueous solutions or buffers containing salts or acids. Also, anion exchange cellulose such as DI-3
2 (Whatman, UK), D) HAE-7μ Low 7
- (manufactured by Braun, West Germany), or anion exchange molecular sieving 1MBfa such as DEAE- or Q
The antibiotic can be adsorbed onto a phase such as AI-Sephadex (manufactured by Pharmasha, Sweden) and eluted with an aqueous solution or buffer solution containing salts or acids. Salts, colored substances, etc. in these eluatesf:'lfI! To remove the particles, use activated carbon for chromatography (manufactured by Taisho Yakuhin Kogyo Co., Ltd., Japan) or adsorbent resins such as Diaion Hp-2o (manufactured by Mitsubishi Kasei Co., Ltd., Japan), Amberlite XAD-II (manufactured by Rohm and Haas Co., Ltd., US → etc. are advantageously used.The fractionated elution section is
1. After going through processes such as agricultural reduction, consolidation, drying and gravel, it is turned into powder. If the powder thus obtained is of poor quality, high performance liquid chromatography is advantageously used for further purification. Examples of carriers used include T8 gel (*Yosoda Co., Ltd., Japan) YMC Ge/I/ (Yamamura Kagaku Kenkyusho, Japan), and the mobile phase is methanol/L' or acetonitrile/ A mixed solution of L' or the like and an acidic aqueous solution or a buffer solution is used.

The TAN-585A thus obtained is usually combined with salts used for purification and cations such as sodium, potassium, lithium, calcium, and ammonium ions in the low f# solution and released as these salts. In order to obtain the obtained TAN-585A salt as a free tetrad, it is common to use activated carbon or cation exchange resin chromatography.

Antibiotic TAN-585A forms metal fields and organic amine salts. Examples of kingen salt include sodium salt,
Examples include potassium salts, lithium salts, calcium salts, and the like.

The physicochemical properties of the disodium-filled 'T'AM-585A obtained in Example 1 described below are as follows.

(1) Appearance: White powder (2) Elemental analysis value -2 (sample dried under reduced pressure over phosphorus pentoxide at 40°C for 6 hours) C460±20 H4,9±1O N 7.0 1.0 0 36.5 ” Na 5.6±1.0 *(However, oxygen is calculated by subtracting other elements) (3) Molecular weight: 8 I L(S (5econdar
The molecular ion peak obtained by the y ion mass spectrometry method is as follows.

m/z 773.751. 729.707 (4) Moisture content: 69% 2% (thermal balance method) (5) Estimated molecular formula (molecular weight): 031F! 36N4o15N&2(750,64)(6
) Circular dichroism spec l-/in water): [θ)22B+2
95,50 (') ± 10,000 ke) Ultraviolet absorption spectrum)/L' (in water) (Fig. 1): λmax 224±
2nm (E'%=312-30) IC shoulder'Amax269±2nm (E'1!=2
5) λmax 277±2nm ()l! = 2
0 person 5. @) (8) Infrared absorption subek)/l/(2nd
Figure): The main absorptions (wave numbers) by potassium bromide are as follows.

3430.3280.2950.1760.1620°1515.1405.1300.1240.1180°1110.1065.1025. 950. 830°760, 600. 535C11-1(9) ”'C
- Nuclear magnetic resonance (CMR) spectrum (100MH2, heavy water): At least the following signals are observed.

1780 value s), 177.60 (a), 171.5 value s
1. 176.88(s).

166.96(a), 166.7dad), 161.01
(s), 159.47(a).

1339 das), 132.76 (s), 132.5 spear +
×2) + 132.4 deposits), 131.33 (d, x2)
, 131.19(s).

119.89 (d, X2), 117.85 (d, X2)
, 103.11(d).

78.99(d), 78.171d1. 75.9 dad
), 75.59(d).

74.53(dl, 74.53(8), 68.07(t
), 63.57(d).

56.22(d), 56.05(t), 32.64(t
) T) pm (However, a: singlet,
d: doublet, t: triplet) io) Solubility: Soluble: water, dimethyl sulfoxide.

Poorly soluble: ethyl acetate, chloroform, acetone.

■ Color reaction: Positive: ninhydrin reaction, Nieprich reagent.

Negative: Brave-Lieback reaction, Burton reaction, Dragendorff reaction.

Stability: 100μ9/1gt + in aqueous solution, 60℃
.

3 hours pH 5-7: Stable pH 3: Moderately unstable pH 9: Unstable 63) Thin layer chromatography Nisbot film,
Cellulose f (manufactured by Tokyo Kasei Co., Ltd.) 14) High performance liquid chromatography (manufactured by Hitachi Co., Ltd. 1 Japan)
: Carrier, YIJC Mu-312 (manufactured by Yamamura Kagaku Kenkyusho 6 Japan), mobile phase; 5% methanol 10.01M phosphate buffer (pH 3.0).

2Ml/win, Rt (win) = 3.3o
S Specific optical rotation: [α] 5-81.6°±15° (
c=056, in water) ao Distinction between acidic, neutral, and basic: Neutral substances (however,
The free form TAN-585A is a malleable material) Next KTAa-5
The biological properties of 85A disodium salt will be described.

This compound has the highest antibacterial spectrum against various microorganisms.
As shown in the table.

wI1 table Pseudomonas aeruginosa 1rFT) 1268
9 1 100 Blue Serratia marsetuscens IN'012648 〉1
00 Acinetobacter Calcaceticus IFV) 13
0116150 Staphylococcus aureus rD
A209P l >100t<fpres-y, jflinu N'I) lJPeI219 1 >100 (Note 1) Medium: Bactoantibiotic Medime 3.17.5
1Fi Bact Yeast Extract, 5g↓Bact Agar.

20g; distilled water; 11; pH 7.0° (Note 2); 106 colony forming units/1d was used as the inoculum solution.

In addition, “rAN585A disodium loading is stable against various β-lactamose.
mirabilis ATCC21100 was used as the test bacterium.
-Illustrate the results of stability studies against lactamase.

Table 2 Note 1) The number fli indicates the diameter of the inhibition circle (mm) measured by the paper disk method. Medium: Nutrient agar medium (pH 7,0
) **: Indicates that there is no blocking effect.

The therapeutic effects of TAN-585A disodium salt on experimental mouse infections are shown in Table 3.
n Despite the weak antibacterial activity in vitro, in
It is an antibiotic that is highly effective in vivo.

Table 3* Intraperitoneal infection; Umbrella* Trypticasa so
yagar(BBL MicrobiologyS
Manufactured by Yatema, USA) @ Ground, 108 as inoculum solution
Colony forming units/stomachs were used.

***Three administrations Furthermore, no acute toxicity was observed when TAN-585A disodium salt was subcutaneously administered to mice at 1 g/dose.

As is clear from these data, it can be said that TAN-585A is an antibiotic that exhibits antibacterial properties mainly against Guhum-negative bacteria and is not toxic to mammals. Therefore, TAN-585A can be used to treat bacterial infections in humans, livestock, poultry, etc.

For example, when TAN-585A is used as a therapeutic agent for Osteoarthritis infection, TAN-585A is dissolved in a saline solution. L, as an injection parenterally subcutaneously or intramuscularly for 1 to 50747KQ 1 day, preferably 17< is 5
~20. , administered on #/day. In addition, as an oral agent, the antibiotic 'dTAN-585A is mixed with lactose to form a capsule, and TAN-5851 is prepared from 1 to IO (1#, :+
7/kQ/day preferably 5-50 m:jl/14
Administer // day.

Moreover, rAIJ-585A obtained by the present invention is
It can be used as a cocoonicide. For example, TAll-
585A from 0.01 to 0. A solution dissolved in distilled water at a concentration of IW/V%, or based on petrolatum, lanolin,
It can be used as an ointment containing 1 g of Adashi TAN-585A, 0.2 to 20 My, preferably 1 to 10 My, for sterilizing and erasing the hands, feet, eyes, ears, etc. of humans and animals.

Antibiotic [TAN-585A is also a very promising compound as a synthetic intermediate for new pharmaceuticals.

Based on the properties described above, antibiotic TAN-585A is considered to be a monozylic β-fuctam antibiotic, but among the known antibiotics belonging to these, the physicochemical properties are relatively similar. Noca
rdicin) group of antibiotics. However, the molecular formula of antibiotic TAN-585A, light external absorption subek)
A/, when comparing the CMR spectrum and antibacterial spectrum with those of nocardicin, it is clearly different, so TAN
-585A is a novel monocyclic β-lactam antibiotic.

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

Percentages are mold cavity/capacity% unless otherwise specified.
shows.

Example 1; Koro 14321) strain was mixed with 2% glucose, 3% soluble starch, 1% raw soybean flour, 1% corn staple liquor, and 1 ton of polype (manufactured by Daigoei Kagaku Co., Ltd.)
500 carp medium in which 0.5% of precipitated acidic μsium was added to an aqueous solution (pH 7.0) containing 0.3% of common salt.
2j Tanisaka Rofwonuko containing the following were inoculated and cultured at 24°C for 48 hours by reciprocating shaking.

The entire amount of this culture solution was added to the medium 30 in which 0.05% of Actco/L/(antifoaming agent, manufactured by Kyushu Yakuhin Kogyo Co., Ltd.) was added to the above medium.
The cells were inoculated into a 501-volume tank containing J and cultured for 48 hours at 24° C. under conditions of aeration rate of 30 j/min and 200 revolutions/min. 6J of this culture solution was added to an aqueous solution (pH 7.0) containing 3% glycero-A, 1.5% raw soybean flour, 1.5% corn gluten meal, and 0.2% polypeptone with precipitated ash. Calcium 0.5%, Actocor/L'0.05%
The cells were inoculated into a tank having a volume of 1t2QOj containing 120J of medium supplemented with the following, and cultured for 66 hours at 24°C under conditions of 120J/min and 150 rotations/min. Culture solution (100j
, pH 6.3) was filtered using Hyflo Super Cell (Johns Manville, USA), and the furnace liquid (88J
) was subjected to IRA-402 (C1 type, 4I) column chromatography. The adsorbed antibiotic was eluted with 1.0M saline (32J), and the eluate was subjected to activated carbon column chromatography (2.5J). 8% activity category
Elution was performed with iso-butanol water (12,5j), and the eluate was subjected to column chromatography using RA-68 (C1 type, 1j). Absorb anti-cocoon substance in 1.0M saline (8j)
The eluate was subjected to activated carbon chromatography (1,
54) for desalting. 1.4 desalted aqueous solution
The concentrated solution was subjected to QAK-Sephadex (A-25, C1 type, 0.4J) column chromatography. The column was diluted with 0.05 M saline (4
After washing with 1.0M saline, the antibiotic was fractionated and eluted with 1.0M saline. The active fractions were collected and subjected to activated carbon column chromatography and eluted with 8% aqueous iso-butanol. The eluate was concentrated under pressure and dried with S phosphorescence, and acetone was added to the lyophilized product to obtain 1.699 of a crude substance.

Cultured in the same manner as above, M111! Crude substance 1 obtained by
．． Combine 42g, dissolve in a small amount of water, and prepare reverse phase carrier M.
It was subjected to preparative high performance chromatography using MC gel. The antibiotic was eluted with 0.01M phosphate buffer (pH 3.0), and the eluate was desalted by activated carbon chromatography. The desalted aqueous solution was compressed under reduced pressure, freeze-dried, and saponified by adding acetone. A white powder (1,34v) of TAN-585A disodium salt was obtained.

[Brief explanation of the drawing]

Figure 1 shows the ultraviolet absorption (L)/L' (in water) of the antibiotic TAN-585A disodium salt, and Figure 2 shows the infrared absorption (L')/L' (KBr method). $1 Ward procedure amendment (voluntary) 1. Indication of the case Patent application No. 40826 of 1982 2, name of the invention Antibiotic TAN-585A, its manufacturing method and new bacterial species of the genus Flexibacter 3, person making the amendment Relationship with the case Patent applicant address Higashi, Osaka City Ward Doshomachi 2-27 Name (29
3) Takeda Pharmaceutical Co., Ltd. Representative: Iku Kurabayashi Department 4, Agent address: 2-17-85 Jusanhonmachi, Yodoyo-ku, Osaka, Tokyo Contact information (Patent Regulations Division) Phone: 278-2219, 2218
6. Contents of amendment 1) “C3□1 (36N40
15Na2 (750-'64-) J r C30
H32! Correct to N4016Na2 (750, t&)J. 2) r 178.09 (El) J on page 17, line 9 of the same book
Insert r 188.46 (s), J in front of ``177゜59 (a) J'' and delete the accompanying letter ``177゜59 (a) J.'' 3) r 132.76 (8) on page 17, line 11 of the same book.
Delete J. 4) 1131.19 (8), page 17, line 12 of the same book,
Delete J. 5) Correct rl and OJ on page 26, line 13 of the same book to ro and IJ. Above 2-

Claims (1)

[Claims] 1. Antibiotic TAN-585A and its salts having the following physicochemical properties as a disodium salt (1) Appearance: white powder (2) Elemental analysis value %, 40°C on phosphorus pentoxide , Sample dried under reduced pressure for 6 hours: C460 Soil 2.0 H4,9±1. ON 7.0±1. O Ha 5.6±10 (3) Molecular weight: 7so+22 (by SIMS method) (
4) Circular dichroism Nuvecto/I/ (in water): [θ]228yo2-95500±10000 (5) Ultraviolet absorption Subek)
/ in water): 1% 1&X 224±2nm (Elc, u-312±30)
-λmax 269±2nm (E”%-25+5)
cti-λmax 277±2nm (p2?,%=2.,
5, 1M) (6) Infrared absorption spec) /L/
: Main absorption due to improved potassium concentration. 3430, 3280.2950. 1760. 16
20°1515, 1405. 1300. 1240
．． 1180°1110, 1065. 1025.
950. 830°760, 600. 5351'1
1 (7) Solubility: Soluble in water, dimethyl sulfoxide,
Poorly soluble in ethyl acetate/L/, chloroform, and acetone (8) Color reaction: positive for ninhydrin and Ehrlich's reagent, negative for Brave-Lieback, Burton, and Dragendorff reactions. 2. Antibiotic TAN-5 belonging to the genus Flexibacter
85A-producing bacteria were cultured in @ ground, and antibiotic T was added to the culture.
A, A method for producing the antibiotic TAN-5851, which comprises producing and accumulating N-5851 and collecting it. 3 Oxidative Fermentative Test is a non-degradable type and has the ability to decompose alginic acid.
Arginoliquefaciens.