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 g cdw À 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.

Stable Isotope-Guided Metabolomics Reveals Polar-Functionalized Fatty-Acylated RiPPs from Streptomyces

“…Various enzymes, including cytochrome P450 monooxygenases, Baeyer–Villiger monooxygenases, − peroxidases, , styrene monooxygenases, and flavoprotein monooxygenase, have been investigated as catalysts for sulfoxidation of aryl sulfides. Although these promiscuous enzymes may be involved in detoxication or degradation of environmental components, several dedicated enzymes involved in the biosynthesis of natural products have been identified .…”

Enantioselective sulfoxidation using Streptomyces glaucescens GLA.0

“…46 A number of BVMOs were able to selectively oxidize mammalian FMO sulde substrates, hence display similar effects on enantioselective preparation of FMOrelated drug metabolites. 18,23,46 Consequently, we believe that S. glaucescens GLA.0 can contribute to studies related to drug metabolism and novel drug development as described before regarding many oxidative enzymes expressed by various Streptomyces species. 47,48 3.3.2 Comparison of sulfoxidation abilities with other Actinobacteria.…”

“…22 Concerning recombinant whole-cell catalysis, recently, AbIMO, a avoprotein monooxygenase from Acinetobacter baylyi ADP1 was heterologously expressed and puried in E. coli and then examined for its sulfoxidation activity. 23 The system produced S-PMSO at 73% yield and high ee (>99.0%) via continuous substrate feeding strategy.…”

Shortening Synthetic Routes to Small Molecule Active Pharmaceutical Ingredients Employing Biocatalytic Methods

“…For this purpose, a recombinant E. coli whole-cell preparation harboring the recombinant styrene monooxygenase from Acinetobacter baylyi was utilized. The development and sulfoxidation activity of this catalyst had been described in a related report …”

“…The development and sulfoxidation activity of this catalyst had been described in a related report. 537…”