Cobalamin‐Dependent Aryl Methyl Ether <i>O</i> ‐Demethylases: Promising Enzymes for Biocatalytic Applications from Lignin Valorization to Organic Synthesis

Abstract Cobalamin‐dependent aryl methyl ether O ‐demethylase is a multi‐component enzyme system that converts O ‐methylated aromatic compounds into demethylated phenolics. The central enzyme of the system is a cobalamin‐dependent protein that interacts with methyltransferase enzymes for transferring the methyl group between O ‐methyl groups of aryl methyl ethers and various methyl acceptors. Besides their role in energy metabolism of certain anaerobic bacteria, O ‐demethylases possess high potential for biocatalysis, including lignin valorization and use in organic synthesis for reversible (de)methylation reactions. An increasing number of cobalamin‐dependent O ‐demethylase enzyme systems from various bacteria, including gut microorganisms, with different substrate scopes and regioselectivity profiles have been identified in the recent decade. Moreover, biocatalytic studies have been carried out on O ‐demethylase systems demonstrating their potential in synthetic applications. In this review, we provide a comprehensive overview of the cobalamin‐dependent aryl methyl ether O ‐demethylase systems identified to date in various microorganisms. We present the mechanism, biological function, substrate scope and selectivity of the studied systems and discuss their potential for biocatalytic applications.