不对称还原α-氨基苯乙酮菌种的筛选及转化条件优化  

Isolation of Microorganisms for Asymmetric Reduction of Prochiral α-aminoacetophenone and Optimization of Reaction Conditions

作　　者：生措[1,2] 任杰[2] 王敏[1] 吴洽庆[2] 朱敦明[2] 

机构地区：[1]天津科技大学生物工程学院,天津300457 [2]中国科学院天津工业生物技术研究所,天津300308

出　　处：《应用与环境生物学报》2012年第2期281-286,共6页Chinese Journal of Applied and Environmental Biology

基　　金：国家重点基础研究发展计划(No.2011CB710801)资助~~

摘　　要：芳香基手性胺醇是许多手性药物合成的重要手性砌块,生物催化不对称还原前手性酮是合成该类醇的重要方法之一.以α-氨基苯乙酮盐酸盐为模型底物从土壤中筛选获得两株能分别高立体选择性催化底物产生R型、S型相应醇的菌株,对映体过量值(e.e.)分别为99%和77%,编号为1403和4802,鉴定菌株所属为镰刀菌属和地霉属.对两株菌培养时期和转化条件的研究表明镰刀菌1403最适生长时间为24 h,最优菌体浓度20 g/L,最优底物浓度5 g/L;地霉4802最适生长时间24 h,最优菌体浓度80 g/L,最优底物浓度3 g/L.底物特异性研究表明,菌株1403和4802均可转化α-氯代苯乙酮、α-溴代苯乙酮、α-羟基苯乙酮和苯乙酮为相应醇,且以α-羟基苯乙酮为底物时,其产物均为S型,e.e.值达99%.Optically active amino alcohols are important building blocks for the synthesis of many chiral pharmaceuticals.A straightforward approach to the synthesis of these chiral amino alcohols is the biocatalytic asymmetric reduction of the corresponding prochiral ketones.Two strains were isolated from soil samples by screening using α-aminoacetophenone as the substrate,and named as 1403 and 4802.Strains 1403 and 4802 reduced α-aminoacetophenone to（R）-and（S）-αaminophenethanol with enantiomeric excess（e.e.） of 99% and 70%,and were identified as Fusarium sp.and Galactomyces sp.,respectively.The conditions for cultivation and biotransformation were optimized.The optimal cultivation time of both strains were 24 h;the optimized concentrations of substrate and resting cell were 5 g/L and 20 g/L for strain 1403（Fusarium sp.）,3 g/L and 80 g/L for strain 4802（Galactomyces sp.）,respectively.Two strains could also convert α-chloroacetophenone,α-bromoacetophenone,and acetophenone to the corresponding alcohols of（R）-and（S）-configuration.Moreover,when α-hydroxyacetophenone was served as substrate（S）-hydroxyphenylethanol was obtained with e.e.of 99% for both strains.

关 键 词：不对称还原 α-氨基苯乙酮 α-氨基苯乙醇 镰刀菌属 地霉属 

分 类 号：TQ920.6[轻工技术与工程—发酵工程]