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.
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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 -
Also Available:Unbound MEDLINE
