JPH0577671B2 - - Google Patents
Info
- Publication number
- JPH0577671B2 JPH0577671B2 JP25622889A JP25622889A JPH0577671B2 JP H0577671 B2 JPH0577671 B2 JP H0577671B2 JP 25622889 A JP25622889 A JP 25622889A JP 25622889 A JP25622889 A JP 25622889A JP H0577671 B2 JPH0577671 B2 JP H0577671B2
- Authority
- JP
- Japan
- Prior art keywords
- tafu
- fraction
- mixture
- microorganisms
- substance
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
- 239000000126 substance Substances 0.000 claims description 19
- 230000000844 anti-bacterial effect Effects 0.000 claims description 11
- 244000005700 microbiome Species 0.000 claims description 10
- 241000228212 Aspergillus Species 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000000284 extract Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 238000000862 absorption spectrum Methods 0.000 description 4
- 125000000457 gamma-lactone group Chemical group 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- 241000228245 Aspergillus niger Species 0.000 description 3
- 244000061456 Solanum tuberosum Species 0.000 description 3
- 235000002595 Solanum tuberosum Nutrition 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229960004793 sucrose Drugs 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000287 crude extract Substances 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 230000035784 germination Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- WNPVZANXRCPJPW-UHFFFAOYSA-N 5-[isocyano-(4-methylphenyl)sulfonylmethyl]-1,2,3-trimethoxybenzene Chemical compound COC1=C(OC)C(OC)=CC(C([N+]#[C-])S(=O)(=O)C=2C=CC(C)=CC=2)=C1 WNPVZANXRCPJPW-UHFFFAOYSA-N 0.000 description 1
- 241000607534 Aeromonas Species 0.000 description 1
- 241000607528 Aeromonas hydrophila Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000123650 Botrytis cinerea Species 0.000 description 1
- 241000222235 Colletotrichum orbiculare Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000223221 Fusarium oxysporum Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- AZLPEJUVWWGLHA-UHFFFAOYSA-N ethyl acetate;hexane;methanol Chemical compound OC.CCCCCC.CCOC(C)=O AZLPEJUVWWGLHA-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 125000000686 lactone group Chemical group 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- YCOFRPYSZKIPBQ-UHFFFAOYSA-N penicillic acid Natural products COC1=CC(=O)OC1(O)C(C)=C YCOFRPYSZKIPBQ-UHFFFAOYSA-N 0.000 description 1
- VOUGEZYPVGAPBB-UHFFFAOYSA-N penicillin acid Natural products OC(=O)C=C(OC)C(=O)C(C)=C VOUGEZYPVGAPBB-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
（産業上の利用分野）
本発明は、γ−ラクトン環を有する新規抗菌性
物質TAFU−567及びその製法に関する。
（従来技術）
従来から、種々の抗菌性物質が微生物により生
産されることが知られており、このうち、アスペ
ルギルス属微生物が生産する抗菌性物質として
は、例えばペニシリン酸〔ケミカル・フアーマシ
ユーテイカル・ブレツテイン、Vol.18、p2259
（1970）〕等が知られている。
しかしながら、従来、アスペルギルス属微生物
が、γ−ラクトン環を有する抗菌性物質を生産す
ることは知られていない。
（発明の構成及び効果）
本発明者らは、鋭意、微生物により生産される
抗菌性物質の検索を行つた結果、アスペルギルス
属に属するある菌株が、γ−ラクトン環を有する
新規抗菌性物質を生産することを見出し、本発明
を完成するに到つた。
即ち、本発明は、次式（）で示されるγ−ラ
クトン環を有する新規抗菌性物質TAFU−567及
びその製法である。
(Industrial Application Field) The present invention relates to a novel antibacterial substance TAFU-567 having a γ-lactone ring and a method for producing the same. (Prior Art) It has been known that various antibacterial substances are produced by microorganisms. Among these, antibacterial substances produced by microorganisms of the genus Aspergillus include, for example, penicillic acid [chemical/pharmaceutical・Bulletstein, Vol.18, p2259
(1970)] are known. However, it has not been known that microorganisms of the genus Aspergillus produce antibacterial substances having a γ-lactone ring. (Structure and Effects of the Invention) As a result of diligently searching for antibacterial substances produced by microorganisms, the present inventors found that a certain strain belonging to the genus Aspergillus produced a novel antibacterial substance having a γ-lactone ring. The present invention was completed based on this discovery. That is, the present invention is a novel antibacterial substance TAFU-567 having a γ-lactone ring represented by the following formula () and a method for producing the same.
【化】
本発明の抗菌性物質TAFU−567は、アスペル
ギルス属に属し、、TAFU−567生産能を有する
微生物を培養し、培養物からTAFU−567を採取
することにより製造することができる。
本発明で使用されるTAFU−567生産菌として
は、アスペルギルス属に属する微生物、例えばア
スペルギルス ニガー NH401があげられる
（微工研菌寄第11002号）。この菌株の諸性状は、
ピツトら著「ア・ラボラトリー・ガイド・トウ
ー・コモン・アスペルギルス・スピーシズ・アン
ド・ゼア・テレオモルフス（1988年、コモンウエ
ルス・サイエンテイフイツク・アンド・インダス
トリアル・リサーチ・オーガニゼーシヨン発行）
等に報告されているアスペルギルス属に属する既
知菌種と比較した結果、アスペルギルス ニガー
のそれに最も近いものであつた。
TAFU−567生産菌の培養は、従来公知の醗酵
生産学的手法に準じ、各種の栄養物質を含む培地
で実施することができる。
培地は、、アスペルギルス属に属し、TAFU−
567生産能を有する微生物が生育できるものであ
れば、特に制限されないが、例えば、馬鈴薯・シ
ヨ糖・寒天培地等の固体培地等を好適に使用する
ことができる。また、培地には、必要に応じ、微
生物の生育を促し、TAFU−567の生産を促進す
る有機物及び無機物を添加することもできる。
培養はPH５〜７、25〜30℃で実施するのが好ま
しい。
培養物中に蓄積したTAFU−567の採取は、醗
酵生産物の採取法として従来公知の方法を適宜選
択、組合わせる等して実施すればよく、例えば次
の如くして実施することができる。即ち、培養終
了後、まず培養物（培地及び／又は菌体）を集
め、有機溶媒（例えばアセトン等）で抽出し、遠
心分離等により抽出液から不溶物を除去後、有機
溶媒を留去する。残渣を水非混和性有機溶媒（例
えば酢酸エチル等）で抽出し、得られる抽出液を
シリカゲルカラムクロマトグラフイー、高速液体
クロマトグラフイー等により分離、精製すること
により、TAFU−567を採取することができる。
上記の如くして得られるTAFU−567の構造
は、当該物質の元素分析、質量分析、紫外線吸収
スペクトル、赤外線吸収スペクトル及び核磁気共
鳴スペクトルにより、前記式（）で示されるγ
−ラクトン環を有する新規化合物であることが明
らかとなつた。
本発明のTAFU−567は優れた抗菌活性を有す
る化合物であり、例えばコレトトリカム ラゲナ
リウム（Colletotrichum lagenarium）、ボツリ
チス シネレア（Botrytis cinerea）、フザリウ
ム オキシスポラム（Fusarium oxysporum）
等の微生物に対し、、これらの微生物の胞子の発
芽を10ppmの濃度で50％以上抑制し、また、
TAFU−567物質は、バチルス ズブチリス
ATCC−6633（Bucillus subtilis ATCC−6633）、
エシエリシアコリ1346（Escherichia coli 1346）
又はアエロモナス リケフアシエンス Ｙ−62
（Aeromonas liquefaciens Ｙ−62）等に対し、
50ppmの濃度でそれらの発芽を抑制した。
実施例
(1) 馬鈴薯200g、シヨ糖200g及び寒天300gから
調製した馬鈴薯・シヨ糖・寒天培地10をシヤ
ーレ500枚に分注し、得られた平板培地上にア
スペルギルス ニガーNH401（微工研菌寄第
11002号）を植菌した後、暗所において24℃で
10日間培養する。培養終了後、菌体及び培地を
集め、アセトン10で２回抽出する。抽出液を
合わせ、アセトンを減圧下に留去した後、水層
を酢酸エチル10で抽出することにより、
TAFU−567の粗抽出液を得る。
(2) (1)で得られた粗抽出液を濃縮し、残渣をシリ
カゲルカラム（5φ×30cm）に付し、ｎ−ヘキ
サンと酢酸エチルとの８：２混液、７：３混
液、６：４混液、５：５混液及び４：６混液の
各500mlで順次溶出を行う。上記４：６混液に
よる溶出画分を集め、溶媒を留去する。残渣を
以下の条件による高速液体クロマトグラフイー
に供する。
カラムサイズ：7.5φ×500mm
担 体：シリカゲル（nucleosil50−５，ケ
ム社製）
溶媒組成：ｎ−ヘキサン−酢酸エチル−メタノ
−ル（550：450：１）
流 速：2.0ml／min
温 度：室温
検出波長：254nm
保持時間18〜19分の画分（以下C1画分という）
及び19〜20分の画分（以下C2画分という）をそ
れぞれを分取する。各画分の比旋光度は次の通り
である。
C1画分：〔α〕20 D＝＋45゜（Ｃ＝0.004、ｎ−ヘキサ
ン−酢酸エチル）
C2画分：〔α〕20 D＝0゜（Ｃ＝0.004、ｎ−ヘキサン
−酢酸エチル）
上記各画分より溶媒を留去することにより、
TAFU−567をC1画分より50mg、C2画分より50mg
を得る。
TAFU−567の理化学的性質は下記第１表の通
りである。なお、前記C1画分とC2画分より同一
物質が得られるのは、TAFU−567が、非極性溶
媒中では、絶対配置及び立体配座の異なる２種の
安定形が存在しうるが、固体状態及び極性溶媒中
では、両者は平衡関係にある混合物として存在す
るためであると思われる。The antibacterial substance TAFU-567 of the present invention can be produced by culturing a microorganism that belongs to the genus Aspergillus and has the ability to produce TAFU-567, and collecting TAFU-567 from the culture. Examples of the TAFU-567-producing bacteria used in the present invention include microorganisms belonging to the genus Aspergillus, such as Aspergillus niger NH401 (Feikoken Bibori No. 11002). The properties of this strain are:
Pitzto et al., A Laboratory Guide to Common Aspergillus Species and Their Teleomorphs (1988, published by the Commonwealth Scientific and Industrial Research Organization)
As a result of comparison with known bacterial species belonging to the genus Aspergillus reported in et al., it was found to be the closest to that of Aspergillus niger. Cultivation of TAFU-567-producing bacteria can be carried out in a medium containing various nutritional substances according to conventionally known fermentation production techniques. The medium belongs to the genus Aspergillus and contains TAFU-
There are no particular restrictions on the medium as long as it allows the growth of microorganisms capable of producing 567, and for example, solid media such as potato, sucrose, and agar media can be suitably used. Furthermore, organic and inorganic substances that promote the growth of microorganisms and the production of TAFU-567 can also be added to the medium, if necessary. Cultivation is preferably carried out at pH 5-7 and 25-30°C. TAFU-567 accumulated in the culture may be collected by appropriately selecting or combining conventionally known methods for collecting fermentation products, and can be performed, for example, as follows. That is, after the completion of cultivation, the culture (medium and/or bacterial cells) is first collected, extracted with an organic solvent (e.g. acetone, etc.), and after removing insoluble matter from the extract by centrifugation etc., the organic solvent is distilled off. . TAFU-567 is collected by extracting the residue with a water-immiscible organic solvent (e.g., ethyl acetate) and separating and purifying the resulting extract by silica gel column chromatography, high-performance liquid chromatography, etc. I can do it. The structure of TAFU-567 obtained as described above was determined by elemental analysis, mass spectrometry, ultraviolet absorption spectrum, infrared absorption spectrum and nuclear magnetic resonance spectrum of the substance, as shown by the above formula ().
-It was revealed that this is a new compound having a lactone ring. TAFU-567 of the present invention is a compound with excellent antibacterial activity, such as Colletotrichum lagenarium, Botrytis cinerea, Fusarium oxysporum.
It suppresses the germination of spores of these microorganisms by more than 50% at a concentration of 10 ppm, and
TAFU-567 substance is Bacillus subtilis
ATCC-6633 (Bucillus subtilis ATCC-6633),
Escherichia coli 1346
or Aeromonas lyquefaciens Y-62
(Aeromonas liquefaciens Y-62) etc.
A concentration of 50 ppm inhibited their germination. Example (1) Potato/sucrose/agar medium 10 prepared from 200 g of potatoes, 200 g of cane sugar, and 300 g of agar was dispensed onto 500 sheets of shear plate, and Aspergillus niger NH401 (Fiber Biotechnology Research Institute) was placed on the resulting plate medium. No.
11002) and then inoculated at 24℃ in the dark.
Incubate for 10 days. After the culture is completed, the cells and medium are collected and extracted twice with 10% acetone. After combining the extracts and distilling off the acetone under reduced pressure, the aqueous layer was extracted with ethyl acetate.
Obtain a crude extract of TAFU-567. (2) Concentrate the crude extract obtained in (1), apply the residue to a silica gel column (5φ x 30cm), and use a mixture of n-hexane and ethyl acetate in an 8:2 mixture, a 7:3 mixture, and a 6:2 mixture. Elution was performed sequentially with 500 ml each of the 4:4 mixture, the 5:5 mixture, and the 4:6 mixture. The eluted fractions from the above 4:6 mixture were collected and the solvent was distilled off. The residue is subjected to high performance liquid chromatography under the following conditions. Column size: 7.5φ x 500mm Support: Silica gel (nucleosil50-5, manufactured by Chem) Solvent composition: n-hexane-ethyl acetate-methanol (550:450:1) Flow rate: 2.0ml/min Temperature: Room temperature Detection wavelength: 254nm Fraction with retention time 18-19 minutes (hereinafter referred to as C 1 fraction)
and the 19-20 minute fraction (hereinafter referred to as C2 fraction). The specific rotation of each fraction is as follows. C 1st fraction: [α] 20 D = +45° (C = 0.004, n-hexane-ethyl acetate) C 2nd fraction: [α] 20 D = 0° (C = 0.004, n-hexane-ethyl acetate) By distilling off the solvent from each of the above fractions,
50mg of TAFU-567 from C1 fraction, 50mg from C2 fraction
get. The physical and chemical properties of TAFU-567 are shown in Table 1 below. The same substance can be obtained from the C1 and C2 fractions because TAFU-567 can exist in two stable forms with different absolute configurations and conformations in a nonpolar solvent. This is thought to be because both exist as a mixture in an equilibrium relationship in the solid state and in a polar solvent.
【表】【table】
第１図は、TAFU−567の紫外線吸収スペクト
ルを、第２図は、同物質の赤外線吸収スペクトル
を、第３図及び第４図は、同物質の核磁気共鳴ス
ペクトル（それぞれ、1H−NMRスペクトル及び
13C−NMRスペクトル）を示す。
Figure 1 shows the ultraviolet absorption spectrum of TAFU-567, Figure 2 shows the infrared absorption spectrum of the same substance, and Figures 3 and 4 show the nuclear magnetic resonance spectrum ( 1H -NMR, respectively) of the same substance. spectrum and
13 C-NMR spectrum).
Claims (1)
力を有する微生物を培養し、培養物からTAFU
−567を採取することを特徴とするTAFU−567
の製法。[Claims] 1. An antibacterial substance TAFU-567 represented by the formula [Formula] or a salt thereof. 2. Cultivate a microorganism that belongs to the genus Aspergillus and has the ability to produce the antibacterial substance TAFU-567 represented by the formula [Formula], and extract TAFU from the culture.
TAFU−567 characterized by collecting −567
manufacturing method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25622889A JPH03118376A (en) | 1989-09-29 | 1989-09-29 | New antibacterial substance tafu-567 and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25622889A JPH03118376A (en) | 1989-09-29 | 1989-09-29 | New antibacterial substance tafu-567 and production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03118376A JPH03118376A (en) | 1991-05-20 |
| JPH0577671B2 true JPH0577671B2 (en) | 1993-10-27 |
Family
ID=17289717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25622889A Granted JPH03118376A (en) | 1989-09-29 | 1989-09-29 | New antibacterial substance tafu-567 and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03118376A (en) |
-
1989
- 1989-09-29 JP JP25622889A patent/JPH03118376A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH03118376A (en) | 1991-05-20 |
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