Radical S-adenosylmethionine (SAM) enzymes use a site-differentiated [4Fe-4S] cluster and SAM to initiate radical reactions through liberation of the 5′-deoxyadenosyl (5′-dAdo•) radical. They form the largest enzyme superfamily, with more than 700,000 unique sequences currently, and their numbers continue to grow as a result of ongoing bioinformatics efforts. The range of extremely diverse, highly regio- and stereo-specific reactions known to be catalyzed by radical SAM superfamily members is remarkable. The common mechanism of radical initiation in the radical SAM superfamily is the focus of this review. Most surprising is the presence of an organometallic intermediate, Ω, exhibiting an Fe–C5′-adenosyl bond. Regioselective reductive cleavage of the SAM S–C5′ bond produces 5′-dAdo• to form Ω, with the regioselectivity originating in the Jahn–Teller effect. Ω liberates the free 5′-dAdo• as the catalytically active intermediate through homolysis of the Fe–C5′ bond, in analogy to Co–C5′ bond homolysis in B12, which was once viewed as biology's choice of radical generator.

中文翻译：

---

自由基 SAM 酶超家族的自由基引发机制

自由基 S-腺苷甲硫氨酸 (SAM) 酶使用位点分化的 [4Fe-4S] 簇和 SAM 通过释放 5'-脱氧腺苷 (5'-dAdo•) 自由基来引发自由基反应。它们构成了最大的酶超家族，目前拥有超过 700,000 个独特序列，并且由于持续的生物信息学努力，它们的数量仍在不断增长。已知由激进 SAM 超家族成员催化的极其多样化、高度区域和立体特异性反应的范围是引人注目的。自由基 SAM 超家族中自由基引发的常见机制是本综述的重点。最令人惊讶的是有机金属中间体 Ω 的存在，它表现出 Fe-C5'-腺苷键。 SAM S–C5' 键的区域选择性还原裂解产生 5'-dAdo• 形成 Ω，其区域选择性源自 Jahn-Teller 效应。 Ω 通过 Fe-C5' 键的均裂释放游离 5'-dAdo• 作为催化活性中间体，类似于 B 中的 Co-C5' 键均裂12，曾被视为生物学对自由基产生剂的选择。