Asymmetric Sulfoxidations Catalyzed by Bacterial Flavin-Containing Monooxygenases

Area of Science:

• Biocatalysis
• Enzymology
• Organic Chemistry

Background:

• Flavin-containing monooxygenases (FMOs) are known biocatalysts for amine and indole oxidation.
• FMOs also exhibit activity towards sulfides, suggesting potential for sulfoxidation reactions.

Purpose of the Study:

• To investigate the utility of methylophaga sp. FMO (mFMO) and its mutants for the enantioselective oxidation of prochiral aromatic sulfides.
• To explore a newly identified thermostable FMO from Nitrincola lacisaponensis (NiFMO) as a biocatalyst.

Main Methods:

• Enzymatic assays using mFMO, its mutants, and NiFMO with various prochiral aromatic sulfides.
• Analysis of product enantioselectivity using chiral separation techniques.

Main Results:

• Both mFMO and NiFMO demonstrated activity towards most tested sulfides.
• The enzymes produced chiral sulfoxides with moderate to high enantioselectivity.
• Enzyme variants displayed distinct enantioselective profiles, indicating substrate pocket influence.

Conclusions:

• mFMO and NiFMO are effective biocatalysts for enantioselective sulfoxidation of prochiral aromatic sulfides.
• Enzyme engineering of mFMO's substrate binding pocket allows for tunable enantioselectivity.
• These findings establish FMOs as versatile tools for asymmetric synthesis of chiral sulfoxides.