Efficient synthesis of (S)-2-chloro-1-(2, 4-dichlorophenyl) ethanol using a tetrad mutant alcohol dehydrogenase from Lactobacillus kefir. (October 2019)

• Record Type: Journal Article
• Authors: Chen, Nan; Chen, Yinyue; Tang, Yunping; Zhao, Qiaoling; Liu, Chenjuan; Niu, Wenwen; Huang, Peiyang; Yu, Fangmiao; Yang, Zuisu; Ding, Guofang
• Is Part Of: Process biochemistry. Volume 85(2019)
• Page Start: 78
• Page End: 83
• Publication Date: 2019-10
• Subjects: Asymmetric reduction -- Alcohol dehydrogenase -- 2-Chloro-1-(2, 4-dichlorophenyl) ethanone -- (S)-2-Chloro-1-(2, 4-dichlorophenyl) ethanol -- Luliconazole; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2019.07.008
• Languages: English
• ISSNs: 1359-5113

Abstract

Graphical abstract: Highlights: A mutant alcohol dehydrogenase (ADH) was first used for producing the luliconazole intermediate. The reaction was catalyzed by this mutant ADH with excellent stereoselectivity (ee 99.5%). Using 50 g/L crude enzyme, 60 g/L substrate was completely reduced in 6 h. Abstract: As the key chiral intermediate of luliconazole, (S)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((S)-CPEO) was prepared from 2-chloro-1-(2, 4-dichlorophenyl) ethanone (CPE) using a tetrad mutant alcohol dehydrogenase (A94T/F147L/L199H/A202L) from Lactobacillus kefir (LK-TADH) coupled with glucose dehydrogenase (GDH). Enzyme-substrate docking simulation was used to reveal the molecular basis of the increases in catalytic ability and enantiomeric excess (ee) values of LK-TADH. Furthermore, using 60 g/L of CPE for gram-scale preparation of (S)-CPEO, the conversion rate reached approximately 100% after 6 h at 35 °C, and the ee value of the final product was 99.5%. Our research provides a foundation for preparing of (S)-CPEO using LK-TADH.