Recent advances in dissecting the demethylation reactions in natural product biosynthesis.

Demethylation is a chemical process widely distributed in nature to remove a methyl group from an organic molecule, which is a key aspect of diverse biological processes including biosynthesis of natural products, degradation of plant biomass and epigenetic regulation. This process is facilitated by diverse demethylases via distinct mechanisms. Recent studies have disclosed some novel demethylation reactions as well as their underlying demethylases in the biosynthesis of bacterial sterols, fungal terpenoids, and plant alkaloids. This article focuses on current advances in dissecting the demethylation reactions in biosynthesis of natural products and aims to point out the enzymatic mechanisms, which will further enhance our knowledge and understanding of demethylation process in nature.