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.

小号-腺苷甲硫氨酸（SAM）在活生物体中无处不在，并且在代谢中作为各种酶的辅助因子具有重要意义。甲基转移酶（MTase）是SAM依赖性酶的主要组成部分，可催化从SAM转移到小分子次级代谢产物和大分子（包括蛋白质和核酸）中的C，O，N和S原子。MTase一直以来一直是生物医学研究中的热门话题，因为它们在大分子的表观遗传调控和具有丰富药理作用部分的天然产物的生物合成中起着至关重要的作用。但是，另一组与SAM共享相似核心结构域的SAM依赖酶可以催化非甲基化反应并具有多种功能。在这里，我们主要描述生物合成中SAM依赖性酶的非甲基化反应。第一的，我们比较了SAM依赖性MTase和非甲基化SAM依赖性酶之间的结构和机理相似性和区别。其次，我们总结了这些酶催化的反应并探讨了机理。最后，我们讨论了类I类非甲基化SAM依赖性酶的结构保守性和催化多样性，并提出了酶进化的可能性，为酶介导的化学和生物技术提出了未来的观点，这将有助于开发新的方法。药物合成。