Development of Microbial Enzymatic Catalysts towards the Chemo-Enzymatic Synthesis of Bioactive Substances

微生物酶催化剂的开发用于生物活性物质的化学酶合成

基本信息

批准号：
14560084
负责人：
SUGAI Takeshi
金额：
$ 2.3万
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：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

An important aspect in the enzyme-catalyzed production of chemicals is the complementary and synergistic use of chemo-enzymatic procedure so that we can draw a reasonable and straightforward blueprint towards the target molecules. Needless to say, a remarkable advantage is that enzymes are the catalysts whose supply from microorganisms, animals, and plants never quit, as the resources can be reproduced in a self-production manner.In this study supported by the grant-in-aid (2002-2003), the achievements were ; 1) lipase-mediated kinetic resolution of heterocyclic amino acids including N-protected forms of proline and N-protected forms of indolinecarboxyolic acid ; 2) Asymmetrization of prochira diketones by means of a yeast (Torulaspora delbrueckii) catalyzed reduction to provide enantiomerically pure cyclic hemiacetals ; 3) Radical-mediated conversion of the cyclic acetals to α-alkenyl-substituted β-hydroxycyclohexanone, which would be the starting material of terpenoids such as tryptocallols and madindolines ; 4) substrate specificity study and long-term preservable cell preparation of the above new biocatalyt, Torulaspora delbrueckii ; 5) combination of electroorganic chemistry (constant current electrolysis) and enzyme-catalyzed desymmetrization of a prochiral diester to give the key intermediate of natural occurring bioactive product, such as helianulol E.

化学物质酶产生的酶产生的一个重要方面是化学酶方法的完整而协同的使用，因此我们可以向目标分子绘制合理且直接的蓝图。不用说，一个显着的优势是，酶是催化剂，其微生物，动物和植物的供应永远不会退出，因为可以自行产生的方式复制资源。在这项研究得到了赠款（2002-2003）支持的这项研究中，成就是； 1）脂肪酶介导的杂环氨基酸的动力学分辨率，包括N保护形式的脯氨酸和N保护形式的吲哚线羧酸； 2）通过酵母（Torulaspora delbrueckii）催化减少prochira二酮的不对称化，以提供对映体纯净的循环半叶子； 3）自由基介导的环状乙酰基向α-烷基苯基取代的β-羟基环己酮的转化，这将是萜类化合物的起始材料，例如甲状腺色素和madindolines； 4）上述新型生物催化剂Torulaspora delbrueckii的底物特异性研究和长期可保存的细胞制备； 5）电机化学（恒定电流电解）和酶催化的酶的降解剂的酶二酯的化学化，从而赋予天然发生的生物活性产物的关键中间体，例如HelianulolE。