Diversity of the reaction mechanisms of SAM-dependent enzymes

S-adenosylmethionine (SAM) is ubiquitous in living organisms and is of great significance in metabolism as a cofactor of various enzymes. Methyltransferases (MTases), a major group of SAM-dependent enzymes, catalyze methyl transfer from SAM to C, O, N, and S atoms in small-molecule secondary metabolites and macromolecules, including proteins and nucleic acids. MTases have long been a hot topic in biomedical research because of their crucial role in epigenetic regulation of macromolecules and biosynthesis of natural products with prolific pharmacological moieties. However, another group of SAM-dependent enzymes, sharing similar core domains with MTases, can catalyze nonmethylation reactions and have multiple functions. Herein, we mainly describe the nonmethylation reactions of SAMdependent enzymes in biosynthesis. First, we compare the structural and mechanistic similarities and distinctions between SAM-dependent MTases and the non-methylating SAM-dependent enzymes. Second, we summarize the reactions catalyzed by these enzymes and explore the mechanisms. Finally, we discuss the structural conservation and catalytical diversity of class I-like non-methylating SAM-dependent enzymes and propose a possibility in enzymes evolution, suggesting future perspectives for enzyme-mediated chemistry and biotechnology, which will help the development of new methods for drug synthesis. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Automated summary

This article mainly describes the importance of non-methylation reactions of SAM-dependent enzymes in biosynthesis, compares the structural and mechanistic similarities and distinctions between SAM-dependent MTases and non-methylating SAM-dependent enzymes, summarizes the reactions catalyzed by these enzymes, and discusses the structural conservation and catalytical diversity of class I-like non-methylating SAM-dependent enzymes. It also proposes a possibility in enzyme evolution and suggests future perspectives for enzyme-mediated chemistry and biotechnology for the development of new methods for drug synthesis.