Li_2021_Adv.Synth.Catal_362_4699

Reference

Title : Reprogramming Epoxide Hydrolase to Improve Enantioconvergence in Hydrolysis of Styrene Oxide Scaffolds - Li_2021_Adv.Synth.Catal_362_4699
Author(s) : Li FL , Qiu YY , Zheng YC , Chen FF , Kong XD , Xu JH , Yu HL
Ref : Adv Synth Catal , 362 :4699 , 2021
Abstract :

Enantioconvergent hydrolysis by epoxide hydrolase is a promising method for the synthesis of important vicinal diols. However, the poor regioselectivity of the naturally occurring enzymes results in low enantioconvergence in the enzymatic hydrolysis of styrene oxides. Herein, modulated residue No. 263 was redesigned based on structural information and a smart variant library was constructed by site-directed modification using an "optimized amino acid alphabet' to improve the regioselectivity of epoxide hydrolase from Vigna radiata (VrEH2). The regioselectivity coefficient (r) of variant M263Q for the R-isomer of meta-substituted styrene oxides was improved 40-63-fold, and variant M263V also exhibited higher regioselectivity towards the R-isomer of para-substituted styrene oxides compared with the wild type, which resulted in improved enantioconvergence in hydrolysis of styrene oxide scaffolds. Structural insight showed the crucial role of residue No. 263 in modulating the substrate binding conformation by altering the binding surroundings. Furthermore, increased differences in the attacking distance between nucleophilic residue Asp101 and the two carbon atoms of the epoxide ring provided evidence for improved regioselectivity. Several high-value vicinal diols were readily synthesized (>88% yield, 90%-98% ee) by enantioconvergent hydrolysis using the reprogrammed variants. These findings provide a successful strategy for enhancing the enantioconvergence of native epoxide hydrolases through key single-site mutation and more powerful enzyme tools for the enantioconvergent hydrolysis of styrene oxide scaffolds into single (R)-enantiomers of chiral vicinal diols.

PubMedSearch : Li_2021_Adv.Synth.Catal_362_4699
PubMedID:
Gene_locus related to this paper: vigra-Vreh3

Related information

Gene_locus vigra-Vreh3
Structure vigra-Vreh3    7CG2    7CG6

Citations formats

Li FL, Qiu YY, Zheng YC, Chen FF, Kong XD, Xu JH, Yu HL (2021)
Reprogramming Epoxide Hydrolase to Improve Enantioconvergence in Hydrolysis of Styrene Oxide Scaffolds
Adv Synth Catal 362 :4699

Li FL, Qiu YY, Zheng YC, Chen FF, Kong XD, Xu JH, Yu HL (2021)
Adv Synth Catal 362 :4699