Enantioselective cascade biocatalysis for deracemization of 2-hydroxy acids using a three-enzyme system

Microbial Cell Factories

Research

Hao Zeng¹  Ya-Ping Xue¹  Yu-Guo Zheng¹  Zhi-Qiang Liu¹  Xiao-Lu Jin² 

[1] Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, 310014, Hangzhou, People’s Republic of China;Yosemade Pharmaceutical Co. Ltd., 321025, Jinhua, People’s Republic of China;

关键词: Coexpression;    Cascade biocatalysis;    Deracemization;    2-hydoxy acids;   

DOI  :  10.1186/s12934-016-0560-1

 received in 2016-05-06, accepted in 2016-09-14,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundEnantiopure 2-hydroxy acids are key intermediates for the synthesis of pharmaceuticals and fine chemicals. We present an enantioselective cascade biocatalysis using recombinant microbial cells for deracemization of racemic 2-hydroxy acids that allows for efficient production of enantiopure 2-hydroxy acids.ResultsThe method was realized by a single recombinant Escherichia coli strain coexpressing three enzymes: (S)-2-hydroxy acid dehydrogenase, (R)-2-keto acid reductase and glucose dehydrogenase. One enantiomer [(S)-2-hydroxy acid] is firstly oxidized to the keto acid with (S)-2-hydroxy acid dehydrogenase, while the other enantiomer [(R)-2-hydroxy acid] remains unchanged. Then, the keto acid obtained reduced to the opposite enantiomer with (R)-2-keto acid reductase plus cofactor regeneration enzyme glucose dehydrogenase subsequently. The recombinant E. coli strain coexpressing the three enzymes was proven to be a promising biocatalyst for the cascade bioconversion of a structurally diverse range of racemic 2-hydroxy acids, giving the corresponding (R)-2-hydroxy acids in up to 98.5 % conversion and >99 % enantiomeric excess.ConclusionsIn summary, a cascade biocatalysis was successfully developed to prepare valuable (R)-2-hydroxy acids with an efficient three-enzyme system. The developed elegant cascade biocatalysis possesses high atom efficiency and represents a promising strategy for production of highly valued (R)-2-hydroxy acids.

【 授权许可】

CC BY   
© The Author(s) 2016