具有非对映选择性还原6-氰基-(5R)-羟基-3-羰基己酸叔丁酯活性的微生物菌株筛选与鉴定  

Screening and Identification of A Strain Displaying Diastereoselective Reductase Activity towards t-Butyl 6-cyano-(5R)-hydroxyl-3-oxohexanoate

作　　者：毛芳芳[1] 王亚军[1] 罗希[1] 魏积福[1] 郑裕国[1] 

机构地区：[1]浙江工业大学生物工程研究所 生物转化与生物净化教育部工程中心,浙江杭州310014

出　　处：《化学与生物工程》2012年第7期12-16,共5页Chemistry & Bioengineering

基　　金：国家重点基础研究发展计划项目(2011CB710800);浙江工业大学教学方法改革专项项目(JGZ1110)

摘　　要：6-氰基-(3R,5R)-二羟基己酸叔丁酯是合成阿托伐他汀钙的关键手性前体。从自然环境中筛选得到一株具有非对映选择性还原6-氰基-(5R)-羟基-3-羰基己酸叔丁酯活性的菌株X25,结合表型特征、生理生化特征和分子遗传学鉴定,确定菌株X25属于季也蒙毕赤酵母(Pichia guilliermondii)。研究了P.guilliermondii X25静息细胞非对映选择性还原6-氰基-(5R)-羟基-3-羰基己酸叔丁酯制备6-氰基-(3R,5R)-二羟基己酸叔丁酯过程。结果表明,最佳催化条件为35℃、pH值7.0;在低底物转化率时,能够制备光学纯6-氰基-(3R,5R)-二羟基己酸叔丁酯。t-Butyl 6-cyano-（3R,5R）-dihydroxyhexanoate is the important chiral building block for atorvasta- tin calcium. A strain X25 possessing moderate diastereoselective ketoreductase activity towards t-butyl 6-cyano- （SR）-hydroxyl-3-oxohexanoate was screened from nature , and identified belonging to Pichia guilliermondii based on phenotypic,physiological and biochemical characteristics and 18S rDNA sequence comparison. A bio- catalytic process for t-butyl 6-cyano-（3R, 5R）-dihydroxyhexanoate was successfully developed with P. guilliermondii X25. Results indicated that its optimal biocatalytic conditions were 35 ℃, pH value of 7.0. Under above conditions, optical pure t-butyl 6-cyano-（3R, 5R）-dihydroxyhexanoate could be prepared at low onversion rate of t-butyl 6-cyano-（5R）-hydroxyl-3-oxohexanoate.

关 键 词：阿托伐他汀钙 6-氰基-(3R 5R)-二羟基己酸叔丁酯 羰基还原酶 季也蒙毕赤酵母 

分 类 号：TQ920.1[轻工技术与工程—发酵工程]