Cmethyltransferases

C-methyltransferases are enzymes that catalyze the transfer of a methyl group to a carbon atom on a substrate, typically using S-adenosyl-L-methionine (SAM) as the methyl donor. They form a subset of methyltransferases that specifically target carbon atoms, in contrast to enzymes that methylate nitrogen, oxygen, sulfur, or other elements.

Mechanistically, many C-methyltransferases belong to the broader methyltransferase superfamily and employ a SAM-binding fold to align the methyl donor for transfer to a carbon center, often via a nucleophilic attack in an SN2-like process. Some C-methyltransferases utilize radical SAM chemistry to enable methylation of particularly unreactive carbon sites, expanding the range of possible substrates.

C-methyltransferases are found in bacteria, fungi, and plants and participate in both primary and secondary metabolism. In secondary metabolism, they contribute to the structural diversification of natural products by installing methyl groups on polyketide or nonribosomal peptide backbones, thereby affecting biological activity and biosynthetic outcomes. In plants, related enzymes participate in the biosynthesis of lignin precursors, pigments, and other metabolites where methylation modulates chemical properties.

Substrate scope among C-methyltransferases varies from highly substrate-specific to broadly permissive, with activity depending on the enzyme’s active-site architecture and cofactors. Their study supports pathway engineering and natural product diversification, enabling the production of methylated compounds with potential pharmaceutical and industrial applications. See also methyltransferase and SAM-dependent methylation.