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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.
Appl Biochem Biotechnol 2019; 188(1):87-100AB

Abstract

(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.

Authors+Show Affiliations

Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai, 201203, China.Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai, 201203, China.Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai, 201203, China.Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai, 201203, China.Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai, 201203, China.Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai, 201203, China. zhangfuli1@sinopharm.com.Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai, 201203, China. chenshaoxin@sinopharm.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30341711

Citation

Tang, Jiawei, et al. "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." Applied Biochemistry and Biotechnology, vol. 188, no. 1, 2019, pp. 87-100.
Tang J, Wei T, Ni G, et al. 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. Appl Biochem Biotechnol. 2019;188(1):87-100.
Tang, J., Wei, T., Ni, G., Guo, X., Wu, Y., Zhang, F., & Chen, S. (2019). 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. Applied Biochemistry and Biotechnology, 188(1), pp. 87-100. doi:10.1007/s12010-018-2904-2.
Tang J, et al. 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. Appl Biochem Biotechnol. 2019;188(1):87-100. PubMed PMID: 30341711.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Tang,Jiawei, AU - Wei,Tengyun, AU - Ni,Guowei, AU - Guo,Xiang, AU - Wu,Yuanjie, AU - Zhang,Fuli, AU - Chen,Shaoxin, Y1 - 2018/10/20/ PY - 2018/07/10/received PY - 2018/10/01/accepted PY - 2018/10/21/pubmed PY - 2019/6/25/medline PY - 2018/10/21/entrez KW - (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol KW - 3,5-bis(trifluoromethyl) acetophenone KW - Carbonyl reductase KW - Leifsonia sp. KW - Response surface methodology SP - 87 EP - 100 JF - Applied biochemistry and biotechnology JO - Appl. Biochem. Biotechnol. VL - 188 IS - 1 N2 - (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. SN - 1559-0291 UR - https://www.unboundmedicine.com/medline/citation/30341711/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 L2 - https://dx.doi.org/10.1007/s12010-018-2904-2 DB - PRIME DP - Unbound Medicine ER -