Screeing of novel microbial- and enzyme catalysts for expeditious chemical synthesis of useful substances

筛选新型微生物和酶催化剂，用于快速化学合成有用物质

基本信息

批准号：
18580106
负责人：
SUGAI Takeshi
金额：
$ 2.49万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18580106/
关键词：
organic chemistry bioreactor enzymes applied microbiology 酸素バイオリアクター

项目摘要

Based on the chemo-enzymatic synthesis with complementary use of organic synthesis and enzyme-catalyzed transformation, the following researches were accomplished.1) Screening of microorganisms which can reduce sterically hindered ketones. in enantifacially selective mannerTowards the synthesis of sterically hindered optically active secondary alcohol, yeast strains (Candida floricola IAM 13115 and)-Trichosporon cutaneum IAM 12206) with si-face hydride attack on isopropyl phenylsulfonylmethyl ketone were newly developed by screening. Strains with complementary re-facial selectivity (Pichia angusta IAM 12895 and Pichia minute IAM 12215) were also found. Based on the substrate specificity studies of these four strains, microbial reduction was applied to the synthesis of (3S, 5S)-2, 6-dimethyl-3, 5-heptanediol.2) Application of newly found yeast strains for the synthesis of naturally occurring bioactive product, such as modiolide A.While the first total synthesis of modiolide A, a ten-membered ring lactone with a marine-origin was achieved, an important chiral building block for constructing the chirality at C-4, (S)-6-[(4-methoxybenzyl)oxy]-1-trimethylsilyl-1-hexyn-3-ol was obtained in as high as 96.1% ee. Asymmetric reduction of a silylated propargyl ketone mediated by whole-cell of Pichia minute IAM 12215 was established.3) Delopment of Bacillus subtilis epoxide hydrolase in organic syntheses.An expeditious route for the enantiopure 2-methylpropane-1, 2, 3-triol monobenzyl ether was examined. An engineered Bacillus subtilis epoxide hydrolase worked enantioselectively on a racemic epoxide to provide the desired product in highly enantiomerically enriched state.

基于化学酶合成，通过互补的使用有机合成和酶催化的转化，完成了以下研究。1）筛选微生物，可以减少在空间上阻碍的酮。在对映射的选择性mannertowards中，酵母菌菌株（Candida Floricola IAM 13115和-Trichosporon Cutaneum IAM 12206）与Si-Face Hydride的氢化氢甲基甲基甲基甲基菌株（Candida Floricola IAM 13115和 - 三磷酸）的合成与异丙基苯基苯基硫基磺酰甲基酮基因酮有关。还发现了具有互补重新选择性的菌株（Pichia angusta iam 12895和Pichia Minute IAM 12215）。 Based on the substrate specificity studies of these four strains, microbial reduction was applied to the synthesis of (3S, 5S)-2, 6-dimethyl-3, 5-heptanediol.2) Application of newly found yeast strains for the synthesis of naturally occurring bioactive product, such as modiolide A.While the first total synthesis of modiolide A, a ten-membered ring lactone with a marine-origin实现了在C-4，（S）-6-- [（（4-甲氧基苯甲酰）氧气中构建手性的重要手性构建块，以高达96.1％EE获得了高达96.1％EE。建立了由Pichia Minute IAM 12215介导的硅胶propargyl酮的不对称减少。3）在有机合成中的枯草杆菌环氧化杆菌水解酶的脱发。在有机合成中。对映射2-甲基丙烷-1，2-甲基propane-1，3- triol monobenbenzyl interoiol monobenzyl intery hythecient。工程设计的枯草芽孢杆菌环氧水解酶对对照式环氧化物的对象征作用，以高度映体富集的状态提供所需的产物。