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Enzymatic synthesis of an ezetimibe intermediate using carbonyl reductase coupled with glucose dehydrogenase in an aqueous-organic solvent system.
Bioresour Technol 2017; 229:26-32BT

Abstract

(4S)-3-[(5S)-5-(4-Fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-ET-5) is an important chiral intermediate in the synthesis of chiral side chain of ezetimibe. Recombinant Escherichia coli expressing carbonyl reductase (CBR) was successfully constructed in this study. The total E. coli biomass and the specific activity of recombinant CBR in 5L fermenter culture were 10.9gDCWL-1 and 14900.3Ug-1DCW, respectively. The dual-enzyme coupled biocatalytic process in an aqueous-organic biphasic solvent system was first constructed using p-xylene as the optimal organic phase under optimized reaction conditions, and 150gL-1 (4S)-3-[5-(4-fluorophenyl)-1,5-dioxophentyl]-4-phenyl-1,3-oxazolidin-2-one (ET-4) was successfully converted to (S)-ET-5 with a conversion of 99.1% and diastereomeric excess of 99% after 24-h, which are the highest values reported to date for the production of (S)-ET-5.

Authors+Show Affiliations

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China.School of Pharmaceutical Engineering, Zhejiang Pharmaceutical College, Ningbo 315100, PR China.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China. Electronic address: zhengyg@zjut.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28092733

Citation

Liu, Zhi-Qiang, et al. "Enzymatic Synthesis of an Ezetimibe Intermediate Using Carbonyl Reductase Coupled With Glucose Dehydrogenase in an Aqueous-organic Solvent System." Bioresource Technology, vol. 229, 2017, pp. 26-32.
Liu ZQ, Dong SC, Yin HH, et al. Enzymatic synthesis of an ezetimibe intermediate using carbonyl reductase coupled with glucose dehydrogenase in an aqueous-organic solvent system. Bioresour Technol. 2017;229:26-32.
Liu, Z. Q., Dong, S. C., Yin, H. H., Xue, Y. P., Tang, X. L., Zhang, X. J., ... Zheng, Y. G. (2017). Enzymatic synthesis of an ezetimibe intermediate using carbonyl reductase coupled with glucose dehydrogenase in an aqueous-organic solvent system. Bioresource Technology, 229, pp. 26-32. doi:10.1016/j.biortech.2016.12.098.
Liu ZQ, et al. Enzymatic Synthesis of an Ezetimibe Intermediate Using Carbonyl Reductase Coupled With Glucose Dehydrogenase in an Aqueous-organic Solvent System. Bioresour Technol. 2017;229:26-32. PubMed PMID: 28092733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzymatic synthesis of an ezetimibe intermediate using carbonyl reductase coupled with glucose dehydrogenase in an aqueous-organic solvent system. AU - Liu,Zhi-Qiang, AU - Dong,Si-Chuan, AU - Yin,Huan-Huan, AU - Xue,Ya-Ping, AU - Tang,Xiao-Ling, AU - Zhang,Xiao-Jian, AU - He,Jun-Yao, AU - Zheng,Yu-Guo, Y1 - 2017/01/06/ PY - 2016/10/28/received PY - 2016/12/23/revised PY - 2016/12/24/accepted PY - 2017/1/17/pubmed PY - 2017/2/28/medline PY - 2017/1/17/entrez KW - Aqueous-organic solvent system KW - Carbonyl reductase KW - Chiral intermediate of ezetimibe KW - Dual-enzyme coupled system KW - Glucose dehydrogenase SP - 26 EP - 32 JF - Bioresource technology JO - Bioresour. Technol. VL - 229 N2 - (4S)-3-[(5S)-5-(4-Fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-ET-5) is an important chiral intermediate in the synthesis of chiral side chain of ezetimibe. Recombinant Escherichia coli expressing carbonyl reductase (CBR) was successfully constructed in this study. The total E. coli biomass and the specific activity of recombinant CBR in 5L fermenter culture were 10.9gDCWL-1 and 14900.3Ug-1DCW, respectively. The dual-enzyme coupled biocatalytic process in an aqueous-organic biphasic solvent system was first constructed using p-xylene as the optimal organic phase under optimized reaction conditions, and 150gL-1 (4S)-3-[5-(4-fluorophenyl)-1,5-dioxophentyl]-4-phenyl-1,3-oxazolidin-2-one (ET-4) was successfully converted to (S)-ET-5 with a conversion of 99.1% and diastereomeric excess of 99% after 24-h, which are the highest values reported to date for the production of (S)-ET-5. SN - 1873-2976 UR - https://www.unboundmedicine.com/medline/citation/28092733/Enzymatic_synthesis_of_an_ezetimibe_intermediate_using_carbonyl_reductase_coupled_with_glucose_dehydrogenase_in_an_aqueous_organic_solvent_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-8524(16)31776-X DB - PRIME DP - Unbound Medicine ER -