Highly Efficient Access to (S)-Sulfoxides Utilizing a Promiscuous Flavoprotein Monooxygenase in a Whole-Cell Biocatalyst Format

Abstract

Chiral sulfoxides have gained attention as synthons and precursors for API synthesis. Flavoproteins such as Baeyer-Villiger or styrene monooxygenases mainly provide access to (R)-sulfoxides and often suffer from low selectivity, activity, and/or limited substrate scope. The flavoprotein monooxygenase AbIMO from Acinetobacter baylyi ADP1 initiates indole degradation. Here, AbIMO was expressed recombinantly in E. coli and characterized for its sulfoxidation activity and substrate spectrum. Next to indole and styrene, AbIMO was found to accept numerous alkyl aryl sulfides as substrates, transforming them to (S)-sulfoxides with high enantioselectivity (95 % to '99 % for most sulfides). The formulation as a whole-cell biocatalyst allowed specific production rates of up to 370 U gcdw−1 – the highest specific oxygenase activity achieved in whole cells so far – and the preparative synthesis of enantiopure (S)-aryl alkyl sulfoxides. With its extraordinarily high specific activity, high specificity, ease of handling, and high stability (catalyst is stable for '16 days at 4 °C), the designed whole-cell biocatalyst adds enormous value to the portfolio of chemical and biological catalysts for asymmetric sulfoxide synthesis.