Scalable biocatalytic synthesis of optically pure ethyl (R)-2-hydroxy-4-phenylbutyrate using a recombinant E. coli with high catalyst yield.

Ye Ni, Yuning Su, Haidong Li, Jieyu Zhou, Zhihao Sun

Index: J. Biotechnol. 168(4) , 493-8, (2013)

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Abstract

Ethyl (R)-2-hydroxy-4-phenylbutanoate [(R)-HPBE] is a versatile and important chiral intermediate for the synthesis of angiotensin-converting enzyme (ACE) inhibitors. Recombinant E. coli strain coexpressing a novel NADPH-dependent carbonyl reductase gene iolS and glucose dehydrogenase gene gdh from Bacillus subtilis showed excellent catalytic activity in (R)-HPBE production by asymmetric reduction. IolS exhibited high stereoselectivity (>98.5% ee) toward α-ketoesters substrates, whereas fluctuant ee values (53.2-99.5%) for β-ketoesters with different halogen substitution groups. Strategies including aqueous/organic biphasic system and substrate fed-batch were adopted to improve the biocatalytic process. In a 1-L aqueous/octanol biphasic reaction system, (R)-HPBE was produced in 99.5% ee with an exceptional catalyst yield (g product/g catalyst) of 31.7 via bioreduction of ethyl 2-oxo-4-phenylbutyrate (OPBE) at 330 g/L.Copyright © 2013 Elsevier B.V. All rights reserved.