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Enzymatic synthesis of an ezetimibe intermediate using carbonyl reductase coupled with glucose dehydrogenase in an aqueous-organic solvent system

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논문

Enzymatic synthesis of an ezetimibe intermediate using carbonyl reductase coupled with glucose dehydrogenase in an aqueous-organic solvent system

학술지

Bioresource technology : biomass, bioenergy, biowastes, conversion technologies, biotransformations, production technologies

저자명

Liu, Z.Q.; Dong, S.C.; Yin, H.H.; Xue, Y.P.; Tang, X.L.; Zhang, X.J.; He, J.Y.; Zheng, Y.G.

초록

(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<SUP>-1</SUP> and 14900.3Ug<SUP>-1</SUP>DCW, 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<SUP>-1</SUP> (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.

발행연도

2017

발행기관

Elsevier Applied Science

ISSN

0960-8524

229

페이지

pp.26-32

주제어

Carbonyl reductase; Glucose dehydrogenase; Chiral intermediate of ezetimibe; Dual-enzyme coupled system; Aqueous-organic solvent system

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논문; 2017-04-01

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