A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors.
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.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China).
Xu-Dong
XD
Kong
Qian
Q
Ma
Jiahai
J
Zhou
Bu-Bing
BB
Zeng
Jian-He
JH
Xu
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry; D001410:Bacillus megaterium / Q000201:enzymology; D055162:Biocatalysis; D020134:Catalytic Domain; D004851:Epoxide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015202:Protein Engineering; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000319:Adrenergic beta-Antagonists; D004851:Epoxide Hydrolases
enantioselectivity; enzyme catalysis; kinetic resolution; protein engineering; structure-activity relationships