Mechanistic Aspects of Methyltransferases with Small-Molecule Metabolites and Natural Products as Substrates

Abstract Methylation is a widely distributed chemical modification on various biomolecules such as small-molecule metabolites and natural products. Enzymatic methylation is mainly catalyzed by methyltransferases with S-adenosyl- l -methionine (SAM) as a methyl donor. A majority of known methylation of small-molecule metabolites and natural products occurs on carbon, oxygen or nitrogen atoms. Methyltransferases can thus be classified according to the atomic types of these methylation nucleophiles. In comparison with the limited nucleophilic atoms as major methyl acceptors, the substrates of methyltransferases often display a broad chemical diversity. The structures of methyltransferases with the substrates of small-molecule metabolites and natural products have often been characterized for a Rossmann-fold architecture. These methyltransferases can thus be categorized according to their catalytic mechanisms. This book chapter will focus on the mechanistic description of these methylation events and the associated methyltransferase activities.