响应面法优化羰基还原酶产生菌Cyberlindnera saturnus发酵培养基  

Medium optimization for carbonyl reductase producing strain Cyberlindnera saturnus by response surface methodology

作　　者：肖美娟 朱治任 刘月旺 王普[1] XIAO Meijuan;ZHU Zhiren;LIU Yuewang;WANG Pu(School of Pharmaceutical Science,Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]浙江工业大学药学院,浙江杭州310014

出　　处：《生物加工过程》2021年第1期47-53,共7页Chinese Journal of Bioprocess Engineering

基　　金：国家自然科学基金(21676250);浙江省自然科学基金(LY16B060010)。

摘　　要：(13R,17S)乙基仲醇是合成甾体类避孕药物左炔诺孕酮的手性中间体,可利用Cyberlindnera saturnus ZJPH1807菌株催化乙基二酮不对称还原制备(13R,17S)乙基仲醇。为进一步提高该菌株的羰基还原酶活力,采用单因素实验和响应面优化法对其发酵培养基中碳源、氮源及无机盐等主要成分和添加量进行优化,得到最优培养基组成(g/L):葡萄糖34.36、酵母膏14.89、NH4Cl30.34、KH2PO41.01。采用优化后的发酵培养基,菌体比酶活达0.27 U/g(以1 g细胞计),生物量为6.13 g/L,分别比优化前提高了233.33%和20.39%,为高效合成左炔诺孕酮提供了基础。(13R,17S)⁃ethyl secols is an important chiral intermediate used in the synthesis of contraceptive levonorgestrel.Cyberlindnera saturnus ZJPH1807 can be used as a biocatalyst for the asymmetric reduction of ethyl secondione to prepare(13R,17S)⁃ethyl secols.To further enhance the carbonyl reductase activity of C.saturnus ZJPH1807,the main components of the fermentation medium including carbon source,nitrogen source,and inorganic salt were optimized using single factor experiment and response surface methodology(RSM).The optimized medium composition was(g/L):glucose 34.36,yeast extract 14.89,NH4 Cl 30.34,KH2 PO41.01.With the optimized medium,enzyme activity reached 0.27 U/g,biomass was 6.13 g/L,with the increase of 233.33%and 20.39%,respectively.The results provide a basis for the efficient synthesis of levonorgestrel by biocatalysis.

关 键 词：(13R 17S)乙基仲醇 Cyberlindnera saturnus 响应面优化 羰基还原酶 甾体药物 左炔诺孕酮 绿色制造 

分 类 号：TQ426􀆰[化学工程]