The radical SAM (S-adenosyl-l-methionine) superfamily is one of the largest group of enzymes with >113000 annotated sequences [Landgraf, B. J., et al. (2016) Annu. Rev. Biochem. 85, 485–514]. Members of this superfamily catalyze the reductive cleavage of SAM using an oxygen sensitive 4Fe-4S cluster to transiently generate 5′-deoxyadenosyl radical that is subsequently used to initiate diverse free radical-mediated reactions. Because of the unique reactivity of free radicals, radical SAM enzymes frequently catalyze chemically challenging reactions critical for the biosynthesis of unique structures of cofactors and natural products. In this Perspective, I will discuss the impact of characterizing novel functions in radical SAM enzymes on our understanding of biosynthetic pathways and use two recent examples from my own group with a particular emphasis on two radical SAM enzymes that are responsible for carbon skeleton formation during the biosynthesis of a cofactor and natural products.

中文翻译：

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天然产物和辅因子生物合成方面的突破

自由基SAM（S-腺苷-1-甲硫氨酸）超家族是最大的一组酶，其注释序列> 113000 [Landgraf，BJ等。（2016）Annu。生物化学牧师。85，485–514]。该超家族的成员使用对氧敏感的4Fe-4S簇催化SAM的还原裂解，以瞬时生成5'-脱氧腺苷基，随后将其用于引发各种自由基介导的反应。由于自由基具有独特的反应性，自由基SAM酶经常催化化学上具有挑战性的反应，这些反应对于辅因子和天然产物独特结构的生物合成至关重要。在这个观点中，我将讨论表征自由基SAM酶的新功能对我们对生物合成途径的理解的影响，并使用我自己小组中的两个最近的例子，其中特别强调了两个自由基SAM酶，这些酶在碳自由基形成过程中起着骨架的作用。辅因子和天然产物的生物合成。