Development of an Efficient and Cost-Effective Enzymatic Process for Production of (R)-[3,5-bis(trifluoromethyl)phenyl] Ethanol Using Carbonyl Reductase Derived from Leifsonia sp. S749

Journal Article · Wed May 15 04:00:00 EDT 2019 · Applied Biochemistry and Biotechnology

DOI:https://doi.org/10.1007/S12010-018-2904-2· OSTI ID:22927762

Tang, Jiawei; Wei, Tengyun; Ni, Guowei; Guo, Xiang; Wu, Yuanjie; Zhang, Fuli; Chen, Shaoxin ^[1]

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1. Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry (China)

(R)-[3,5-bis(trifluoromethyl) phenyl] ethanol [(R)-3,5-BTPE] is a crucial chiral intermediate for the synthesis of the NK-1 receptor antagonists aprepitant, rolapitant and fosaprepitant. The carbonyl reductase KR01 from Leifsonia sp. S749, discovered by protein sequence alignment, could convert 3′,5′-bis(trifluoromethyl) acetophenone (3,5-BTAP) into (R)-3,5-BTPE with excellent activity and enantioselectivity. In order to enhance the conversion efficiency at high substrate concentrations, the reaction conditions were optimized by response surface analysis. The results showed that 600 g/L 3,5-BTAP was bioreduced to (R)-3,5-BTPE (> 99.9% enantiomeric excess) by the recombinant Escherichia coli/pET-28a (+)-KR01 whole cells, with a 98.3% conversion and 59 g/L/h productivity under the optimized reaction conditions. In addition, the recombinant E. coli cells could be repeatedly used up to seven times in the reaction mixture containing 90% isopropanol (IPA). This is the highest substrate loading and productivity for the bioreduction of 3,5-BTAP by carbonyl reductase ever reported, and this method represents an efficient and cost-effective process for production of (R)-3,5-BTPE.

• OSTI ID: 22927762
• Journal Information: Applied Biochemistry and Biotechnology, Journal Name: Applied Biochemistry and Biotechnology Journal Issue: 1 Vol. 188; ISSN 0273-2289; ISSN ABIBDL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETOPHENONE
CARBONYLS
ESCHERICHIA COLI
ETHANOL
OXIDOREDUCTASES
RECEPTORS
SYNTHESIS