Issue 95, 2022

Engineering of a Baeyer–Villiger monooxygenase reveals key residues for the asymmetric oxidation of omeprazole sulfide

Abstract

The structure-guided engineering of a BVMO from Rhodococcus aetherivorans (RaBVMO) was performed for its asymmetric sulfoxidation activity toward omeprazole sulfide. Based on the structural model of RaBVMO, key residues that line the substrate entrance tunnel and the binding pocket were identified, and variants were interrogated with sulfides of varied sizes. The best mutant MT2 (F442A/R337P) was obtained with a specific activity of 2.54 U g−1 and excellent enantioselectivity (≥99%, S) toward omeprazole sulfide, while wild-type RaBVMO exhibited no activity. Further structural analysis reveals that both mutations, F442A and R337P, could render an expanded substrate tunnel and an enlarged substrate binding pocket to enable easier access to the catalytic center for omeprazole sulfide. This work provides valuable guidance for engineering-related BVMOs for improved activity and enantio-preference toward bulky substrates.

Graphical abstract: Engineering of a Baeyer–Villiger monooxygenase reveals key residues for the asymmetric oxidation of omeprazole sulfide

Supplementary files

Article information

Article type
Communication
Submitted
28 Jul 2022
Accepted
29 Oct 2022
First published
31 Oct 2022

Chem. Commun., 2022,58, 13246-13249

Engineering of a Baeyer–Villiger monooxygenase reveals key residues for the asymmetric oxidation of omeprazole sulfide

S. Wei, G. Xu, L. Zhang, J. Zhou and Y. Ni, Chem. Commun., 2022, 58, 13246 DOI: 10.1039/D2CC04161H

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