JPS6319155B2 - - Google Patents
Info
- Publication number
- JPS6319155B2 JPS6319155B2 JP15989580A JP15989580A JPS6319155B2 JP S6319155 B2 JPS6319155 B2 JP S6319155B2 JP 15989580 A JP15989580 A JP 15989580A JP 15989580 A JP15989580 A JP 15989580A JP S6319155 B2 JPS6319155 B2 JP S6319155B2
- Authority
- JP
- Japan
- Prior art keywords
- metal salt
- lactone type
- lactone
- type
- fusarium
- 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
Links
- 150000002596 lactones Chemical class 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 18
- WWSNTLOVYSRDEL-DZSDEGEFSA-N compactin diol lactone Chemical compound C([C@@H]1[C@H]2[C@@H](O)CCC=C2C=C[C@@H]1C)C[C@@H]1C[C@@H](O)CC(=O)O1 WWSNTLOVYSRDEL-DZSDEGEFSA-N 0.000 claims description 17
- WWSNTLOVYSRDEL-UHFFFAOYSA-N desmethylmonacolin J Natural products CC1C=CC2=CCCC(O)C2C1CCC1CC(O)CC(=O)O1 WWSNTLOVYSRDEL-UHFFFAOYSA-N 0.000 claims description 17
- 229910052751 metal Inorganic materials 0.000 claims description 16
- 239000002184 metal Substances 0.000 claims description 16
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 12
- 244000005700 microbiome Species 0.000 claims description 7
- 239000000284 extract Substances 0.000 claims description 6
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 claims description 5
- 241000223218 Fusarium Species 0.000 claims description 5
- 241000228143 Penicillium Species 0.000 claims description 4
- 241000371644 Curvularia ravenelii Species 0.000 claims description 3
- 241000235395 Mucor Species 0.000 claims description 3
- 241000235527 Rhizopus Species 0.000 claims description 3
- 239000000126 substance Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000000862 absorption spectrum Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241001623528 Mucor circinelloides f. griseocyanus Species 0.000 description 3
- 241000228150 Penicillium chrysogenum Species 0.000 description 3
- 241000235546 Rhizopus stolonifer Species 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 241000190150 Bipolaris sorokiniana Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000427940 Fusarium solani Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 235000002233 Penicillium roqueforti Nutrition 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- -1 hydroxy-3-methylglutaryl coenzyme A Chemical compound 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000013028 medium composition Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
本発明は微生物変換によりML―236B（ラクト
ン型または金属塩）よりML―236A（ラクトン型
または金属塩）を製造する方法に関するものであ
る。
ML―236Bは既知物質であり、青カビの一種ペ
ニシリウム・チトリヌムの代謝産物より分離、精
製された物質で、実験動物から分離した酵素系や
培養細胞系においてコレステロールの生合成をそ
の律速酵素の３―ヒドロキシ―３―メチルグルタ
リルコエンザイムＡリダクターゼと競合すること
により阻害し、動物の個体レベルにおいても強力
な血清コレステロールの低下作用を示すことが知
られている（特開昭50−155690号、ジヤーナル・
オブ・アンチビオテイクス29巻1346〜1348頁
1976年）。
ML―236Bは次の化学構造を有する。
The present invention relates to a method for producing ML-236A (lactone form or metal salt) from ML-236B (lactone form or metal salt) by microbial conversion. ML-236B is a known substance, isolated and purified from the metabolites of Penicillium titrinum, a type of blue mold. It is known that it inhibits hydroxy-3-methylglutaryl coenzyme A reductase by competing with it, and exhibits a strong serum cholesterol-lowering effect even at the individual animal level (Japanese Patent Application Laid-open No. 155690/1989, Journal
of Antibiotics, Vol. 29, pp. 1346-1348.
(1976). ML-236B has the following chemical structure.
【式】または[expression] or
【式】
なお、本発明において「ML―236B」にはその
金属塩（特開昭53−56314号）も含む。ML―
236Aもまた既知物質であり、次の化学構造を有
し、同様にラクトン型および酸型が知られている
（特開昭51−136885）。[Formula] In the present invention, "ML-236B" also includes its metal salt (Japanese Patent Application Laid-Open No. 53-56314). ML―
236A is also a known substance and has the following chemical structure, and the lactone type and acid type are also known (Japanese Patent Application Laid-open No. 136885-1985).
【式】または[expression] or
【式】
そして、本発明において「ML―236A」にはそ
の金属塩も含む。
本発明は微生物変換によりML―236B（ラクト
ン型または金属塩）よりML―236A（ラクトン型
または金属塩）を製造する方法に関するものであ
る。
本発明を実施するには、ML―236B（ラクトン
型または金属塩）をML―236A（ラクトン型また
は金属塩）に変換せしめ得る能力を有するペニシ
リウム属、フザリウム属、ヘルミントスポリウム
属、ムコール属またはリゾプス属に属する微生物
を、ML―236B（ラクトン型または金属塩）を含
有する培地で培養するか或いはこれらの微生物の
無細胞抽出液をML―236B（ラクトン型または金
属塩）に作用せしめればよい。
本発明において用いうる微生物としてはML―
236B（ラクトン型または金属塩）をML―236A
（ラクトン型または金属塩）に変換せしめ得る能
力を有するペニシリウム属、フザリウム属、ヘル
ミントスポリウム属、ムコール属またはリゾプス
属に属する微生物が用いられるが、本発明者らが
特に有効であると認める菌株は
ペニシリウム・クリソゲナム（Penicillium
chrysogenum） ATCC 10002
フザリウム・リニ（Fusarium Iini） SANK
10561 （微工研菌寄第5768号）
フザリウム・ソラニ（Fusarium solani）
SANK 23073 （微工研菌寄第5770号）
ヘルミントスポリウム・サテイバム
（Helminthosporium sativum） SANK
11558 （微工研菌寄第5767号）
ムコール・グリゼオシアヌス（Mucor griseo
−cyanus） IFO 4563
リゾプス・ニグリカンス（Rhizopus
nigricans） NRRL 45
ペニシリウム・チトリヌム（Penicillum
citrinum） SANK 18767 （微工研菌寄第
2609号）
があげられる。これらの菌株はいづれも微工研に
寄託されているか、もしくは公的な菌保存機関
（ATCC，IFOもしくはNRRL）より入手可能で
ある。
なお、微生物変換により得られた化合物は化学
的常法に従つて、例えば金属塩を酸で処理するこ
とによりラクトン型に変換することができる。
本発明の方法において得られるML―236Aは側
鎖に適当なアシル基を導入することにより、ML
―236Bに優るコレステロール阻害活性の増強が
期待されるので、動脈硬化、高脂血症など体内に
おけるコレステロールの蓄積が原因の一つである
疾病の予防あるいは治療用医薬の原料として有用
である。
次に実施例を示す。
実施例 １
下記組成の培地100mlを含有する500ml容坂口フ
ラスコ20本にペニシリウム・クリソゲナムATCC
10002を植菌し、26℃、120s.p.mで振盪培養し、
４日後、ML―236B Na塩を最終濃度で0.05％に
なるように添加して更に３日間26℃、120s.p.m.
で培養する。
培地組成
グルコース 2.0％
K2HPO4 0.15
MgSO4・7H2O 0.15
NH4NO3 0.1
ペプトン 0.1
C.S.L 0.2
イーストエキストラクト 0.1
ZnSO4 0.001
水道水 残
（PH7.0に調整）
得られた培養液を過し、液1.9を得た。
これを6N―HClでPH4.0として、２の酢酸エチ
ルで抽出した。抽出液を硫酸ナトリウムを用いて
脱水し、次いで触媒量のトリフルオロ酢酸を添加
してラクトン化した。次いで抽出液を５％炭酸水
素ナトリウム水溶液で洗浄後、濃縮乾固して得た
油状物934mgを10ｇのシリカゲル（ワコーゲルＣ
―200）のカラムに吸着させた。カラムをｎ―ヘ
キサン100ml、ｎ―ヘキサン：アセトン（85：15）
200mlの順で展開した。さらにカラムを200mlのア
セトンで展開するとML―236A画分が溶出され
る。この画分を濃縮乾固してML―236A（ラクト
ン型）435mgを採取した。
本化合物は薄層クロマトグラフイー（TLC）
（TLCプレート；メルク社製シリカゲルArt5715、
溶媒；ｎ―ヘキサン：アセトン＝１：１）では
Rf0.21を示す。
ML―236A（ラクトン型）の物理化学的性質は
以下に記述する如くである。
本物質は白色粉末状の中性物質で、質量分析に
よる分子量は306で分子式はC18H26O4である。本
物質の紫外部吸収スペクトルを第１図に、赤外部
吸収スペクトルを第２図に示す。これらの物理化
学的データは既に報告されている特開昭51−
136885号のML―236A（ラクトン型）のデータと
全て一致した。
実施例 ２
フザリウム・リニ SANK 10561を用い、実
施例１と同様に操作してML―236A（ラクトン型）
を得た。
実施例 ３
フザリウム・ソラニ SANK 23073を用い、
実施例１と同様に操作してML―236A（ラクトン
型）を得た。
実施例 ４
ヘルミントスポリウム・サテイバム
SANK11558を用い、実施例１と同様に操作して
ML―236A（ラクトン型）を得た。
実施例 ５
ムコール・グリゼオシアヌス IFO 4563を用
い、実施例１と同様に操作してML―236A（ラク
トン型）を得た。
実施例 ６
リゾプス・ニグリカンス NRRL 45を用いて
実施例１と同様に操作してML―236A（ラクトン
型）を得た。
なお、実施例２乃至実施例６で用いた培地は実
施例１で用いた培地と同じである。
実施例 ７
ペニシリウム・クリソゲナム ATCC10002を
実施例１の培地に植菌し、26℃、120spmで振盪
培養し、２日後４℃で集菌した。次いで、リン酸
緩衝液（PH7.5、0.1M）に懸濁し、ケイ砂で摩砕
し、冷却遠心機（5000×ｇ）に付し、上清を得
た。得られた上清を無細胞抽出液として以下の反
応に供した。
無細胞抽出液0.5mlおよびML―236BNa塩１ｍ
Ｍを30℃で２時間反応後、薄層クロマトグラフイ
ー（吸着剤；シリカゲルプレートArt5715（メル
ク社製）、展開溶剤；クロロホルム：エタノー
ル：酢酸＝５：１：１）に付して展開するとRf
値0.5にML―236ANa塩のスポツトが確認され
た。
紫外部吸収スペクトル（H2O）
λmax （nm）＝229，236，245[Formula] In the present invention, "ML-236A" also includes its metal salt. The present invention relates to a method for producing ML-236A (lactone form or metal salt) from ML-236B (lactone form or metal salt) by microbial conversion. To carry out the present invention, Penicillium, Fusarium, Helminthosporium, and Mucor species capable of converting ML-236B (lactone form or metal salt) to ML-236A (lactone form or metal salt) are used. Alternatively, microorganisms belonging to the genus Rhizopus can be cultured in a medium containing ML-236B (lactone type or metal salt), or cell-free extracts of these microorganisms can be allowed to act on ML-236B (lactone type or metal salt). Bye. Microorganisms that can be used in the present invention include ML-
236B (lactone type or metal salt) to ML-236A
Microorganisms belonging to the genus Penicillium, Fusarium, Helminthosporium, Mucor, or Rhizopus that have the ability to convert the The bacterial strain is Penicillium chrysogenum.
chrysogenum) ATCC 10002 Fusarium Iini SANK
10561 (Fiber Engineering Research Institute No. 5768) Fusarium solani
SANK 23073 (Helminthosporium sativum) SANK
11558 (Fiber Engineering Research Institute No. 5767) Mucor griseocyanus (Mucor griseocyanus)
−cyanus) IFO 4563 Rhizopus nigricans (Rhizopus
nigricans) NRRL 45 Penicillum titrinum (Penicillum)
citrinum) SANK 18767
No. 2609). All of these strains have been deposited with the Microtech Institute or are available from public bacterial repositories (ATCC, IFO, or NRRL). In addition, the compound obtained by microbial conversion can be converted into a lactone type according to a conventional chemical method, for example, by treating a metal salt with an acid. ML-236A obtained by the method of the present invention is produced by introducing an appropriate acyl group into the side chain.
Since it is expected to have enhanced cholesterol inhibitory activity superior to -236B, it is useful as a raw material for pharmaceuticals for the prevention or treatment of diseases such as arteriosclerosis and hyperlipidemia, which are caused by the accumulation of cholesterol in the body. Next, examples will be shown. Example 1 Penicillium chrysogenum ATCC was added to 20 500 ml Sakaguchi flasks containing 100 ml of a medium with the following composition.
10002 and cultured with shaking at 26℃ and 120s.pm.
After 4 days, ML-236B Na salt was added to a final concentration of 0.05% and incubated at 26°C for another 3 days at 120s.pm.
Cultivate with Medium composition Glucose 2.0% K 2 HPO 4 0.15 MgSO 4・7H 2 O 0.15 NH 4 NO 3 0.1 Peptone 0.1 CSL 0.2 Yeast extract 0.1 ZnSO 4 0.001 Tap water Remainder (adjusted to PH7.0) The obtained culture solution was filtered. Then, liquid 1.9 was obtained.
This was adjusted to pH 4.0 with 6N-HCl and extracted with 2 ethyl acetate. The extract was dehydrated using sodium sulfate and then lactonized by adding a catalytic amount of trifluoroacetic acid. Next, the extract was washed with a 5% aqueous sodium bicarbonate solution, concentrated to dryness, and 934 mg of the obtained oil was added to 10 g of silica gel (Wako Gel C).
-200) column. Column with 100ml of n-hexane, n-hexane:acetone (85:15)
200 ml was developed in this order. Furthermore, when the column is developed with 200 ml of acetone, the ML-236A fraction is eluted. This fraction was concentrated to dryness to collect 435 mg of ML-236A (lactone type). This compound was tested using thin layer chromatography (TLC).
(TLC plate; Merck silica gel Art5715,
Solvent: n-hexane: acetone = 1:1)
Shows R f 0.21. The physicochemical properties of ML-236A (lactone type) are as described below. This substance is a neutral substance in the form of a white powder, with a molecular weight of 306 according to mass spectrometry and a molecular formula of C 18 H 26 O 4 . The ultraviolet absorption spectrum of this substance is shown in Figure 1, and the infrared absorption spectrum is shown in Figure 2. These physicochemical data have already been reported in JP-A-51-
All data matched with the data of ML-236A (lactone type) in No. 136885. Example 2 Using Fusarium linii SANK 10561, ML-236A (lactone type) was prepared in the same manner as in Example 1.
I got it. Example 3 Using Fusarium solani SANK 23073,
The same procedure as in Example 1 was carried out to obtain ML-236A (lactone type). Example 4 Helminthosporium sativum
Using SANK11558, operate in the same manner as in Example 1.
ML-236A (lactone type) was obtained. Example 5 ML-236A (lactone type) was obtained using Mucor griseocyanus IFO 4563 in the same manner as in Example 1. Example 6 ML-236A (lactone type) was obtained using Rhizopus nigricans NRRL 45 in the same manner as in Example 1. Note that the culture medium used in Examples 2 to 6 is the same as the culture medium used in Example 1. Example 7 Penicillium chrysogenum ATCC10002 was inoculated into the medium of Example 1, cultured with shaking at 26°C and 120 spm, and harvested at 4°C two days later. Next, it was suspended in phosphate buffer (PH7.5, 0.1M), ground with silica sand, and subjected to a refrigerated centrifuge (5000xg) to obtain a supernatant. The obtained supernatant was used as a cell-free extract for the following reaction. 0.5ml of cell-free extract and 1ml of ML-236BNa salt
After reacting M at 30°C for 2 hours, it was developed using thin layer chromatography (adsorbent: silica gel plate Art5715 (Merck), developing solvent: chloroform:ethanol:acetic acid = 5:1:1) to obtain Rf.
A spot of ML-236ANa salt was confirmed at a value of 0.5. Ultraviolet absorption spectrum (H 2 O) λmax (nm) = 229, 236, 245
第１図はML―236A（ラクトン型）の紫外部吸
収スペクトルを示し、第２図は同物質の赤外部吸
収スペクトルを示す。
Figure 1 shows the ultraviolet absorption spectrum of ML-236A (lactone type), and Figure 2 shows the infrared absorption spectrum of the same substance.
Claims (1)
ML―236A（ラクトン型または金属塩）に変換せ
しめ得る能力を有するペニシリウム属、フザリウ
ム属、ヘルミントスポリウム属、ムコール属また
はリゾプス属に属する微生物をML―236B（ラク
トン型または金属塩）を含有する培地で培養する
か、或いは該微生物の無細胞抽出液をML―236B
（ラクトン型または金属塩）に作用せしめること
を特徴とするML―236A（ラクトン型または金属
塩）の製造法。1 ML-236B (lactone type or metal salt)
Microorganisms belonging to the genus Penicillium, Fusarium, Helminthosporium, Mucor, or Rhizopus that have the ability to convert into ML-236A (lactone type or metal salt) containing ML-236B (lactone type or metal salt) Either culture the microorganism in a medium containing ML-236B, or use a cell-free extract of the microorganism
(Lactone type or metal salt).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15989580A JPS5783290A (en) | 1980-11-13 | 1980-11-13 | Preparation of ml-236a and its derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15989580A JPS5783290A (en) | 1980-11-13 | 1980-11-13 | Preparation of ml-236a and its derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5783290A JPS5783290A (en) | 1982-05-25 |
| JPS6319155B2 true JPS6319155B2 (en) | 1988-04-21 |
Family
ID=15703513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15989580A Granted JPS5783290A (en) | 1980-11-13 | 1980-11-13 | Preparation of ml-236a and its derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5783290A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11007966B2 (en) * | 2018-06-25 | 2021-05-18 | Toyoda Gosei Co., Ltd. | Head protecting airbag device |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4997848A (en) | 1987-10-27 | 1991-03-05 | Sankyo Company, Limited | Octahydronaphthalene oxime derivatives for cholesterol synthesis inhibition |
| WO2009077523A2 (en) * | 2007-12-18 | 2009-06-25 | Dsm Ip Assets B.V. | Improved statin production |
| JP6059465B2 (en) | 2012-08-14 | 2017-01-11 | 株式会社マーレ フィルターシステムズ | Electric dual pump |
-
1980
- 1980-11-13 JP JP15989580A patent/JPS5783290A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11007966B2 (en) * | 2018-06-25 | 2021-05-18 | Toyoda Gosei Co., Ltd. | Head protecting airbag device |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5783290A (en) | 1982-05-25 |
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