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 metabol...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383520306936 |
| _version_ | 1818848342609756160 |
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| author | Qiu Sun Mengyuan Huang Yuquan Wei |
| author_facet | Qiu Sun Mengyuan Huang Yuquan Wei |
| author_sort | Qiu Sun |
| collection | DOAJ |
| description | 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 enzyme-mediated chemistry and biotechnology, which will help the development of new methods for drug synthesis. |
| first_indexed | 2024-12-19T06:15:49Z |
| format | Article |
| id | doaj.art-3fcc12c991d74de598d9adeb7caeb067 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-19T06:15:49Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-3fcc12c991d74de598d9adeb7caeb0672022-12-21T20:32:52ZengElsevierActa Pharmaceutica Sinica B2211-38352021-03-01113632650Diversity of the reaction mechanisms of SAM-dependent enzymesQiu Sun0Mengyuan Huang1Yuquan Wei2Corresponding author. Tel.: +86 28 85421753; fax: +86 28 85164060.; State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, ChinaState Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, ChinaState Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, ChinaS-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 enzyme-mediated chemistry and biotechnology, which will help the development of new methods for drug synthesis.http://www.sciencedirect.com/science/article/pii/S2211383520306936SAM-dependent enzymeCatalytic mechanismBiocatalysisNonmethylation reactionMethyltransferase |
| spellingShingle | Qiu Sun Mengyuan Huang Yuquan Wei Diversity of the reaction mechanisms of SAM-dependent enzymes Acta Pharmaceutica Sinica B SAM-dependent enzyme Catalytic mechanism Biocatalysis Nonmethylation reaction Methyltransferase |
| title | Diversity of the reaction mechanisms of SAM-dependent enzymes |
| title_full | Diversity of the reaction mechanisms of SAM-dependent enzymes |
| title_fullStr | Diversity of the reaction mechanisms of SAM-dependent enzymes |
| title_full_unstemmed | Diversity of the reaction mechanisms of SAM-dependent enzymes |
| title_short | Diversity of the reaction mechanisms of SAM-dependent enzymes |
| title_sort | diversity of the reaction mechanisms of sam dependent enzymes |
| topic | SAM-dependent enzyme Catalytic mechanism Biocatalysis Nonmethylation reaction Methyltransferase |
| url | http://www.sciencedirect.com/science/article/pii/S2211383520306936 |
| work_keys_str_mv | AT qiusun diversityofthereactionmechanismsofsamdependentenzymes AT mengyuanhuang diversityofthereactionmechanismsofsamdependentenzymes AT yuquanwei diversityofthereactionmechanismsofsamdependentenzymes |