Identification of MsrA homologues for the preparation of (R)-sulfoxides at high substrate concentrations?

Organic & Biomolecular Chemistry Pub Date: 2019-03-04 DOI: 10.1039/C9OB00384C

Abstract

Here we report a methionine sulfoxide reductase A (MsrA) homologue with extremely high substrate tolerance and a wide substrate scope for the biocatalytic preparation of enantiopure sulfoxides. This MsrA homologue which was obtained from Pseudomonas alcaliphila (named paMsrA) showed good activity and enantioselectivity towards a series of aryl methyl/ethyl sulfoxides 1a–1k, with electron-withdrawing or electron-donating substituents at the aromatic ring. Chiral sulfoxides in the R configuration were prepared with approximately 50% of yield and up to 99% enantiomeric excess through the asymmetric reductive resolution of racemic sulfoxide catalyzed by the recombinant paMsrA protein. More importantly, kinetic resolution has been successfully accomplished with high enantioselectivity (E > 200) at initial substrate concentrations up to 320 mM (approximately 45 g L?1), which represents a great improvement in the aspect of the substrate concentration for the biocatalytic preparation of chiral sulfoxides.

Graphical abstract: Identification of MsrA homologues for the preparation of (R)-sulfoxides at high substrate concentrations
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