Qiu Sun, Mengyuan Huang, Yuquan Wei. Diversity of the reaction mechanisms of SAM-dependent enzymes[J]. Acta Pharmaceutica Sinica B, 2021, 11(3): 632-650

Diversity of the reaction mechanisms of SAM-dependent enzymes
Qiu Sun, Mengyuan Huang, Yuquan Wei
State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
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 SAM-dependent 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 enzymemediated chemistry and biotechnology, which will help the development of new methods for drug synthesis.
Key words:    SAM-dependent enzyme    Catalytic mechanism    Biocatalysis    Nonmethylation reaction    Methyltransferase   
Received: 2020-05-11     Revised: 2020-07-30
DOI: 10.1016/j.apsb.2020.08.011
Funds: This work was supported by the National Natural Science Foundation of China (Grant No. 21702141).
Corresponding author: Qiu Sun
Author description:
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Qiu Sun
Mengyuan Huang
Yuquan Wei

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