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

• Published in: Organic & biomolecular chemistry Vol. 17; no. 13; pp. 3381 - 3388
• Main Authors: Yang, Jiawei, Wen, Yuanmei, Peng, Liaotian, Chen, Yu, Cheng, Xiaoling, Chen, Yongzheng
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 27.03.2019; Royal Society of Chemistry
• Subjects: Aromatic compounds; Chemistry; Chemistry, Organic; Enantiomers; Homology; Methionine; Physical Sciences; Proteins; Reductase; Science & Technology; Substrates; Sulfoxides; METHIONINE SULFOXIDE REDUCTASE; ASYMMETRIC-SYNTHESIS; OXIDASE; KINETIC RESOLUTION; DEOXYGENATION; DMSO REDUCTASE; RACEMIC SULFOXIDES; CHIRAL SULFOXIDES; PROCHIRAL SULFIDES; BIOCATALYSIS
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c9ob00384c

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.