A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors

Xu-Dong Kong; Qian Ma; Jiahai Zhou; Bu-Bing Zeng; Jian-He Xu

doi:10.1002/anie.201402653

A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors

Angew Chem Int Ed Engl. 2014 Jun 23;53(26):6641-4. doi: 10.1002/anie.201402653. Epub 2014 May 19.

Authors

Xu-Dong Kong¹, Qian Ma, Jiahai Zhou, Bu-Bing Zeng, Jian-He Xu

Affiliation

¹ State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China).

PMID: 24841567
DOI: 10.1002/anie.201402653

Abstract

Microtuning of the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward bulky substrates.

Keywords: enantioselectivity; enzyme catalysis; kinetic resolution; protein engineering; structure-activity relationships.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic beta-Antagonists / chemical synthesis*
Adrenergic beta-Antagonists / chemistry
Bacillus megaterium / enzymology
Biocatalysis
Catalytic Domain
Epoxide Hydrolases / chemistry
Epoxide Hydrolases / genetics
Epoxide Hydrolases / metabolism*
Protein Engineering
Stereoisomerism
Structure-Activity Relationship
Substrate Specificity

Substances

Adrenergic beta-Antagonists
Epoxide Hydrolases