WO1985004408A1 - Antibiotic tan-588, process for its preparation, and novel strainbelonging to genus empedobacter - Google Patents

Antibiotic tan-588, process for its preparation, and novel strainbelonging to genus empedobacter Download PDF

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Publication number
WO1985004408A1
WO1985004408A1 PCT/JP1984/000150 JP8400150W WO8504408A1 WO 1985004408 A1 WO1985004408 A1 WO 1985004408A1 JP 8400150 W JP8400150 W JP 8400150W WO 8504408 A1 WO8504408 A1 WO 8504408A1
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WO
WIPO (PCT)
Prior art keywords
antibiotic
culture
water
solution
genus
Prior art date
Application number
PCT/JP1984/000150
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
Hideo Ono
Yukimasa Nozaki
Setsuo Harada
Original Assignee
Takeda Chemical Industries, Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Takeda Chemical Industries, Ltd. filed Critical Takeda Chemical Industries, Ltd.
Priority to PCT/JP1984/000150 priority Critical patent/WO1985004408A1/ja
Priority to EP85301948A priority patent/EP0157544A3/en
Priority to US06/714,084 priority patent/US4656288A/en
Priority to ES541441A priority patent/ES8702428A1/es
Priority to DK135785A priority patent/DK135785A/da
Priority to JP60065870A priority patent/JPS615792A/ja
Priority to CA000477912A priority patent/CA1238594A/en
Priority to HU851207A priority patent/HU194310B/hu
Publication of WO1985004408A1 publication Critical patent/WO1985004408A1/ja
Priority to ES555584A priority patent/ES8707251A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
    • C12P1/04—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes by using bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales

Definitions

  • the present invention relates to a novel * antibiotic-poor TA H-588 or a method for producing the same.
  • V, ⁇ , Kuta This is related to the genus of fresh green onion.
  • the present inventors found that a large number of microorganisms were isolated from soil for the purpose of searching for new antibiotics and praised the antibiotics produced by them. Is a new bacterium a belonging to the genus Endobacta, the bacterium is cultivated in an appropriate medium to have antibacterial activity against gram-positive and gram-negative bacteria. Know t and 3 ⁇ 4! Isolate the antibiotic poor, and, based on its physicochemical and biological properties, determine that the antibiotic is a new antibiotic poor 2: -Call it 588
  • the present inventors have further studied based on these findings, and as a result, completed the present invention.
  • the present invention provides a method for culturing (i) an antibiotic TA H-588 and its soil, and (2) an antibiotic-poor TA H-583-producing bacterium belonging to the genus Endopacta in a medium, and adding the antibiotic to the culture. Substances that accumulate and remove substances Prospects TAN-588 and its production method, Prabini (3) D 2 ⁇ ⁇ () C
  • the antibiotic T AF-588 is sometimes referred to as “TA H-588J” in this paper.
  • Antibiotic guest T AH-588-producing bacteria used in the present invention include those belonging to the genus Dempactor (Empedo & ⁇ 3se63:>) and having the ability to produce the antibiotic H AH-538. For example, any new species may be used.
  • 258 strains of Endobacta and Pactumgenus taken by the present inventors from the soil in Masuda City, Shimabane Prefecture >.
  • the mycological properties of the r ⁇ -258 strain are as follows:
  • the cells were cultured for 24 days and observed for 1 to 14 days.
  • Co--1 is translucent pale yellow, round, head-shaped, and all-round. Diffusible dyes are generated.
  • Liquid broth cultivation A turbid state is produced and sedimentation occurs, forming a fungus.
  • Juice gelatin stab culture Grows mainly in the upper part and liquefies like a crater. Liquefaction activity is relatively weak.
  • the properties of the bacterium of the present invention used in the present invention vary within a single coat, for example, ultraviolet rays, X-rays, and chemicals (eg, ⁇ -sogazine, ethyl methanesulfonate). : TA 2T-which is easily mutated by the artificial mutation means to be used and which is a target of the present invention regardless of any mutant strain
  • carbon sources include, for example, g / cos, pratose, matos, sob starch, dextrin, oils and fats (eg, soybean oil, Olive oil *, etc., and organic acids (eg, citric acid, succinic acid, quinone, etc.) Those that can be degraded by bacteria can be used as appropriate.
  • Organic nitrogen compounds such as soybean flour, cottonseed flour, corn gum, dried yeast, yeast extract, meat extract, butane, and urea can be used as the nitrogen bristles.
  • inorganic resources include those required for culturing normal bacteria, such as sodium iodide, potassium bromide, potassium charcoal, magnesium sulfate, phosphorous potassium, and disodium phosphate. Are used alone or in combination as appropriate.
  • Heavy metals such as ferrous nitrate and copper sulfate, vitamins such as vitamin B, and biotin are also added as necessary. Further, it is possible to add any antifoaming agent or surfactant to the medium. It assists the growth of the bacillus and promotes the production of Taw-588: ⁇ Organic and inorganic substances may be added as appropriate.
  • the cultivation method may be the same as the general method for producing antibiotics. ⁇ Solid culture or greed culture may be used. In the case of liquid culture, stationary culture, stirring culture, shaking culture, and aeration culture * l is preferred.
  • the culture temperature is preferably in the range of about 53 ⁇ 4 to 32 'C, and the pH of the culture medium is in the range of about 8:00 to 1 ⁇ 8 hours, preferably about 8 hours.
  • the antibiotic T588 has the property of a water-soluble substance, and is mainly contained in the culture broth. Then, the obtained culture solution is brought into contact with a suitable carrier to absorb the active ingredient in the filtrate, and then the active substance is poorly desorbed with a suitable solvent. Activated carbon, lizard, powdered cellulosic, absorbent resin, etc. Use the difference in the adsorbability of the chemical compound as the carrier for ⁇ - chromatography, or use an anion exchange resin, anion cell mouth, etc.
  • the combination varies depending on the type of the carrier and the method used.
  • aqueous solutions of water-soluble organic solvents such as aqueous acetone and aqueous acetone
  • -A kind of water such as a kind, or an aqueous solution containing an alkali, an alkali, or an inorganic or organic substance, is used in an appropriate combination.
  • a 7t high-performance liquid ⁇ -matographi for crude separation of the 7-t antibiotic obtained from these chromatographs can be further purified.
  • Eluents that have been desalted by hot injection charcoal chromatography-Concentrate and concentrate from concentrates to extract ion-pair- * * 4 4 akian *-organic containing tam'halide This antibiotic can be recovered with a solvent.
  • Anion exchange bases such as DE-32 (Bettman, UK), DE AE-cellose (Brown, West Germany), etc., or ⁇ ion ⁇ molecular sieve resin such as DEA ⁇ - or AE-Sepua Tas (7-Amaya Co., Ltd., Susa-Den) * Any carrier K
  • This antibiotic can be adsorbed and eluted with a plant or an acid-containing aqueous solution or killing solution.
  • Activated carbon for chromatography Takeda Pharmaceutical Co., Japan
  • adsorptive resin such as Diaion HP-20 (Mitsubishi Kasei Co., Japan)
  • Amberlite-: a manufactured by Mouth & Haas Co., USA
  • TSK gel manufactured by Toyo Soda Co., Japan
  • TMC gel manufactured by Yamamura Chemical Laboratory, Japan
  • Yamamura Chemical Laboratory Japan
  • a mixed solution of methano or acetate-toluene with an aqueous solution or a buffer solution is used, which is used in the above-mentioned ion pair extraction method.
  • organic solvents usually include methylene chloride, kloform and dimethyi.
  • ⁇ AH-588 exists in the purification process in a state where it has been used, and whisper ions in the buffer solution, such as sodium, force 9 um, lithium, force ⁇ um, and aluminum ions.
  • the active chromosome at ⁇ 5 as it is, is isolated as the corresponding chromosome when applied to the chromatogram, and preferably 35 to 2 preferably. It is eluted and adjusted to 34.5 to 3 and then subjected to activated carbon chromatography to obtain a free form.
  • Soluble i-water, dimethyl poxide Soluble i-water, dimethyl poxide.
  • Butanol drunk acid r water (1: t: 1) 0.77
  • Bacto-anti-ibidium medium 3 (Di 73., Bo, Trees, USA); 17.5 f, pact, yeast extract (Difco, bottle) 50 f, Park agar (Di7., Bottles, U.S.A.); 20 f, distilled water; 1 000 W (no pH adjustment) Approximately 10 ⁇ cores-one forming unit for Zeifr.
  • ⁇ AH -588 exhibits antibacterial properties against Gram-positive bacteria and Gum-negative bacteria, is toxic to mammals, and is a 4 antibiotic. Therefore, ⁇ AH-5S8 can be used for the treatment of bacterial infections in humans, livestock, and poultry. .
  • ⁇ AN-588 As a treatment for Staphylococcus aureus infection, for example !: A-588 dissolved in physiological saline and injected parenterally subcutaneously or intramuscularly Administer i ⁇ 5 Q ⁇ Z * / day, preferably 5-20 ⁇ Z days.
  • the antibiotic ITTH-588 is mixed with lactose to form a capsule, which is administered at a rate of 1 to 100 W / ⁇ / day, preferably 5 to 5 fl days.
  • ⁇ AH-588 obtained by the present invention can be used for sterilization.
  • ⁇ -583 ⁇ 0.01-9.
  • FIG. 1 shows the ultraviolet absorption spectrum (in water) of the antibiotic Air-588 obtained in Example 1
  • FIG. 2 shows the infrared absorption spectrum ( ⁇ Br method).
  • Lactamgenus y K-258 CFERMP-NA IF 0 1 4322 infested on nutrient agar slope, Glucose 2%, Norbu starch 3 *, Raw soy flour 1, Polybuton (manufactured by Daigo Nutrition Chemical Co., Ltd.) 0.5 ,, food 0.3 * 3 ⁇ 4: aqueous solution (pH 7.0) * C3 ⁇ 4 ⁇ ⁇ -based carbon 0.5 * 3: added
  • the culture medium was inoculated into a two-volume flask containing 50 media, and cultured at 24 for 48 hours.
  • This culture solution S 3 ⁇ 4 dextrin 3 *, raw soybean flour, ⁇ 5 » corn 'glutinme 1.5. *, ⁇ Lipeptone 0 ⁇ 2 *, chio Inoculate a 200-volume tank containing 20 media containing actoco-0.0 * in an aqueous solution (H8.5) containing 0.1 sodium sulfate.
  • the concentrated aqueous solution was concentrated in chromatograms and buoys (50 to 8, The eluate was concentrated and freeze-dried to obtain a crude powder 1.4159.
  • the crude powder (! .4) was dissolved in water (100 W), and the dissolved solution * ⁇ 3 ⁇ 4AE-Sephade -Tas A-1 25 (Type C1, manufactured by Fuarma, Su-Den) was subjected to 20-force sammak chromatography and eluted and fractionated with 0.03 M saline. After adjusting to 1, the mixture was extracted with activated charcoal chromatography, and the eluate was dried and freeze-dried to obtain powder (0. 38). This powder was dissolved in water and used as a carrier.
  • Aqueous solution containing 258 beads (FE ER P-k: IF 0 1 4322) fr g — s 2 » solv tarch 3 «, ⁇ *: soy flour, po 9 ⁇ buton 0.55%, food 0. ⁇ 7. 0) to inoculation with sedimentary carbonate calcium ⁇ beam 0.5 * 2 volumes slope
  • Ropurasu 3 2 containing medium 50 was ⁇ and heavy cultured wrenched 4 3 ⁇ 4 time reciprocation at 24.
  • the whole amount of this culture solution was inoculated into a 200-capacity tank containing the medium ⁇ 20 ⁇ 3 ⁇ 4 supplemented with defoamed Actco-0.05 in the above medium, and aerated at 200 ZZ for 50 times at 24'C.
  • this culture solution S0 is dextrin 3%.
  • Raw soybean flour 1.5, corn 'Guyin-mi, 5th article, polypeptone 0 * 1%, chio A tank with a capacity of 2,000 containing a medium containing 200 mg of actoco ( ⁇ .05) added to a narrow aqueous solution (pa 6.5) containing sodium 0.1 ⁇ 1
  • the cells were cultured for 30 hours under the conditions of 205 rotations / minute.
  • Adetas (C1 type) Attached to the power of 20, mata matog and buoy.
  • the fraction was eluted and fractionated with 0 ⁇ 0311 food water to obtain an active fraction (1, 3).
  • the active fraction was subjected to an operation using activated carbon chromatography, and the eluate was concentrated and freeze-dried to obtain -588 white powder (3.5S f).
  • about 50 * antibiotics remained in the extraction wastewater layer, and it was 0, which was applied to the water layer (5) ⁇ £ -separadex ((; type 1) 1 ⁇ power, muk e matogpi).
  • the antibiotic AH-588 and its antibacterial effect on Gram-positive bacteria and sexual activity such as by oral or non-periodic administration of I 0 to humans and animals ⁇ It can be used for the treatment of

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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PCT/JP1984/000150 1984-03-29 1984-03-29 Antibiotic tan-588, process for its preparation, and novel strainbelonging to genus empedobacter WO1985004408A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
PCT/JP1984/000150 WO1985004408A1 (en) 1984-03-29 1984-03-29 Antibiotic tan-588, process for its preparation, and novel strainbelonging to genus empedobacter
EP85301948A EP0157544A3 (en) 1984-03-29 1985-03-20 Antibiotics, their production and use
US06/714,084 US4656288A (en) 1984-03-29 1985-03-20 Antibiotics, their production and use
ES541441A ES8702428A1 (es) 1984-03-29 1985-03-21 Un metodo para producir antibiotico tan-588 y-o n-desacetil-antibiotico tan-588
DK135785A DK135785A (da) 1984-03-29 1985-03-26 Fremgangsmaade til fremstilling af et antibiotisk stof
JP60065870A JPS615792A (ja) 1984-03-29 1985-03-28 抗生物質およびその製造法
CA000477912A CA1238594A (en) 1984-03-29 1985-03-29 Antibiotics, tan-558, their production and use
HU851207A HU194310B (en) 1984-03-29 1985-03-29 Process for preparing alkali metal, alkali earth metal, ammonium salt and n-deacetylated derivative of novel tan-588 antibiotic
ES555584A ES8707251A1 (es) 1984-03-29 1986-06-02 Un metodo para producir n-desacetil-antibiotico tan-588

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP1984/000150 WO1985004408A1 (en) 1984-03-29 1984-03-29 Antibiotic tan-588, process for its preparation, and novel strainbelonging to genus empedobacter

Publications (1)

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WO1985004408A1 true WO1985004408A1 (en) 1985-10-10

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PCT/JP1984/000150 WO1985004408A1 (en) 1984-03-29 1984-03-29 Antibiotic tan-588, process for its preparation, and novel strainbelonging to genus empedobacter

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JP (1) JPS615792A (enrdf_load_stackoverflow)
CA (1) CA1238594A (enrdf_load_stackoverflow)
DK (1) DK135785A (enrdf_load_stackoverflow)
WO (1) WO1985004408A1 (enrdf_load_stackoverflow)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3108089C2 (de) * 1981-03-04 1987-01-15 Focke & Co, 2810 Verden Vorrichtung zum Auftragen von Leim auf Lappen von Verpackungen
DE4241176B4 (de) * 1992-12-08 2005-12-22 Focke & Co.(Gmbh & Co. Kg) Vorrichtung zum Auftragen von Leim auf Zuschnitte für Klappschachteln
US11459924B2 (en) 2014-09-03 2022-10-04 Corning Incorporated Honeycomb body having layered plugs and method of making the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Shadan Hojin Nippon Yakugakkai Pharmacia Review Henshu Iinkai "Pharmacia Review No. 7, Kosei Busshitsu" (1981-10-15) Shadan Hojin Nippon Yakugakkai, P.2 - 5 and P.16 - 17 *

Also Published As

Publication number Publication date
DK135785D0 (da) 1985-03-26
JPH0582398B2 (enrdf_load_stackoverflow) 1993-11-18
CA1238594A (en) 1988-06-28
DK135785A (da) 1985-09-30
JPS615792A (ja) 1986-01-11

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