Search

Optically pure sulfoxides are valuable organosulfur compounds extensively employed in medicinal and organic synthesis. In this study, we present a biocatalytic oxidation‐reduction cascade system designed for the preparation of enantiopure sulfoxides. The system involves the cooperation of a low‐enantioselective chimeric oxidase SMO (styrene monooxygenase) with a high‐enantioselective reductase MsrA (methionine sulfoxide reductase A), facilitating "non‐selective oxidation and selective reduction" cycles for prochiral sulfide oxidation. The regeneration of requisite cofactors for MsrA and SMO was achieved via a cascade catalysis process involving three auxiliary enzymes, sustained by cost‐effective D‐glucose. Under the optimal reaction conditions, a series of heteroaryl alkyl, aryl alkyl and dialkyl sulfoxides in R configuration were synthesized through this "one‐pot, one step" cascade reaction. The obtained compounds exhibited high yields of >90 % and demonstrated enantiomeric excess (ee) values exceeding 90 %. This study represents an unconventional and efficient biocatalytic way in utilizing the low‐enantioselective oxidase for the synthesis of enantiopure sulfoxides. [ABSTRACT FROM AUTHOR]

Optically pure sulfoxides are noteworthy compounds applied in a wide range of industrial fields; however, the biocatalytic deracemization of racemic sulfoxides is challenging. Herein, a high‐enantioselective methionine sulfoxide reductase A (MsrA) was combined with a low‐enantioselective styrene monooxygenase (SMO) for the cyclic deracemization of sulfoxides. Enantiopure sulfoxides were obtained in >90 % yield and with >90 % enantiomeric excess (ee) through dynamic "selective reduction and non‐selective oxidation" cycles. The cofactors of MsrA and SMO were subsequently regenerated by the cascade catalysis of three auxiliary enzymes through the consumption of low‐cost D‐glucose. Moreover, this "one‐pot, one‐step" cyclic deracemization strategy exhibited a wide substrate scope toward various aromatic, heteroaromatic, alkyl and thio‐alkyl sulfoxides. This system proposed an efficient strategy for the green synthesis of chiral sulfoxide. [ABSTRACT FROM AUTHOR]

Methionine sulfoxide reductase A (MsrA) has emerged as promising biocatalysts in the enantioselective kinetic resolution of racemic (rac) sulfoxides. In this study, we engineered robust MsrA variants through directed evolution, demonstrating substantial improvements of thermostability. Mechanism analysis reveals that the enhanced thermostability results from the strengthening of intracellular interactions and increase in molecular compactness. Moreover, these variants demonstrated concurrent improvements in catalytic activities, and notably, these enhancements in stability and activity collectively contributed to a significant improvement in enzyme substrate tolerance. We achieved kinetic resolution on a series of rac -sulfoxides with high enantioselectivity under initial substrate concentrations reaching up to 93.0 g/L, representing a great improvement in the aspect of the substrate concentration for biocatalytic preparation of chiral sulfoxide. Hence, the simultaneously improved thermostability, activity and substrate tolerance of MsrA represent an excellent biocatalyst for the green synthesis of optically pure sulfoxides. [Display omitted] [ABSTRACT FROM AUTHOR]