度洛西汀中间体生物转化菌株研究  

Screening,identification and cultivation of microorganisms for preparation of duloxetine chiral intermediate

作　　者：欧志敏[1] 杨策[1] 杨根生[1] 

机构地区：[1]浙江工业大学药学院,浙江杭州310014

出　　处：《浙江工业大学学报》2016年第3期340-345,共6页Journal of Zhejiang University of Technology

基　　金：浙江省自然科学基金资助项目(LY15B060005)

摘　　要：(S)-DHTP是合成抗抑郁药物度洛西汀的关键手性中间体,采用微生物土壤筛菌法从土壤中筛选得到一株能够将DKTP不对称地还原为(S)-DHTP的菌株,26SrDNA序列分析鉴定,该菌株属于假丝酵母属,命名为热带假丝酵母Candida tropicalis zjut 22.该菌株能够高效地还原DKTP生成度洛西汀关键手性中间体,底物转化率>90%,(S)-DHTP对映体过量值e.e.>99%,相比于化学法,生物转化合成反应条件更温和而且对环境的污染小.利用单因素和正交试验对其培养基进行优化,菌体干菌质量浓度可达14g/L(菌体干重/发酵液体积).（S）-DHTP is key chiral intermediate for synthesis of duloxetine.A biotransformation method was used to screen fungus from soil in order to obtain a fungus capable of reducing N,Ndimethyl-3-keto-3-（2-thienyl）-1-propanamine（DKTP）to（S）-DHTP,a key precursor to synthesize duloxetine.A fungus was obtained which was capable of asymmetrically reduce DKTP to（S）-DHTP with high yield（more than 90%）and high enantiometric excess（more than 99%）.The DNA sequence of 26 SrDNA identification showed that the fungus belong to the Genus of Candida,and was named as Candida tropicalis zjut 22.The screened fungus could efficiently and asymmetrically reduce DKTP to（S）-DHTP.Compared with the chemical method,the reaction conditions of the microbial transformation are mild and environmentally friendly.The medium content was optimized by Univariate Orthogona and Orthogonal experimental analysis.The concentration of cells can reach up to 14g/L（cell dry weight/volume of fermentation）.

关 键 词：度洛西汀 生物转化法 (S)-DHTP 热带假丝酵母 

分 类 号：R971.43[医药卫生—药品]