Diversity of the reaction mechanisms of SAM-dependent enzymes.
Diversity of the reaction mechanisms of SAM-dependent enzymes.
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SAM依赖性酶反应机制的多样性
DOI：
10.1016/j.apsb.2020.08.011
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Wei Y
中科院分区：
文献类型：
--
作者：
Sun Q;Huang M;Wei Y
S-腺苷蛋氨酸广泛存在于生物体内，作为多种酶的辅因子在代谢中具有重要意义。甲基转移酶(MTase)是一类主要的SAM依赖酶，它催化SAM向小分子次生代谢物和大分子(包括蛋白质和核酸)中的C、O、N和S原子的甲基转移。长期以来，MTase一直是生物医学研究的热点，因为它们在大分子的表观遗传调节和具有丰富药理活性的天然产物的生物合成中起着至关重要的作用。然而，另一类依赖SAM的酶与MTase具有相似的核心结构域，可以催化非甲基化反应，并具有多种功能。在这里，我们主要描述SAM依赖的酶在生物合成中的非甲基化反应。首先，我们比较了SAM依赖的MTase和非甲基化的SAM依赖的酶在结构和机制上的相似和区别。其次，我们总结了这些酶催化的反应，并对其机理进行了探讨。最后，我们讨论了类非甲基化SAM依赖的酶的结构保守性和催化多样性，并提出了酶进化的可能性，提出了酶介导的化学和生物技术的未来前景，这将有助于开发新的药物合成方法。非甲基化的S-腺苷蛋氨酸依赖的酶与甲基转移酶具有相似的核心结构域，但通过不同的机制催化多种反应，参与构建重要的生物活性化合物。对这些酶的结构、催化机理和进化进行综述，有助于酶介导的生物技术和药物合成新方法的发展。长期以来，SAM依赖的酶一直是生物医学研究的热点。SAM依赖的酶具有相似的结构，但可以催化构建重要生物活性化合物所涉及的多种反应。本文综述了SAM依赖的酶催化非甲基化的研究进展。
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. Non-methylating S-adenosylmethionine (SAM)-dependent enzymes share similar core domain with methyltransferases but catalyze versatile reactions through different mechanisms involved in building significant bioactive compounds. The review on structure, catalytic mechanism and evolution of these enzymes may help the development of enzyme-mediated biotechnologies and new methods for drug synthesis. SAM-dependent enzymes have long been a hot topic in biomedical research. SAM-dependent enzymes share structural similarity but can catalyze versatile reactions involved in building important bioactive compounds. The review focuses on SAM-dependent enzymes that catalyze non-methylation.
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影响因子：
56.9
作者：
DEAN, AM;KOSHLAND, DE
通讯作者：
KOSHLAND, DE
影响因子：
3.2
作者：
DECKER, H;MOTAMEDI, H;HUTCHINSON, CR
通讯作者：
HUTCHINSON, CR
影响因子：
--
作者：
Kim J;Almo SC
通讯作者：
Almo SC
影响因子：
4.1
作者：
Abicht, Helge K.;Martinez, Jacobo;Solioz, Marc
通讯作者：
Solioz, Marc
DOI：
10.1016/j.bbrc.2017.08.119
发表时间：
2018-03-29
影响因子：
3.1
作者：
Defelipe, Lucas A.;Osman, Federico;Turjanski, Adrian G.
通讯作者：
Turjanski, Adrian G.