C-C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products.
C-C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products.
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DOI：
10.1039/c8np00006a
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发表时间：
2018-07-18
影响因子：
11.9
通讯作者：
Lilla EA
中科院分区：
文献类型：
--
作者：
Yokoyama K;Lilla EA
C-C键的形成通常是辅因子和天然产物生物合成的关键步骤。历史上，C-C键的形成被认为是通过两种电子机制进行的，以脂肪酸中的Claisen缩合和聚酮生物合成为代表。这些类型的机制需要活化的底物来产生亲核试剂和亲电试剂。最近，越来越多的由自由基SAM酶催化的C-C键形成被发现。这些自由基介导的反应可以在几乎任何sp3和sp2碳中心之间进行，允许在代谢物的非常规位置引入C-C键。因此，自由基介导的C-C键形成经常被发现在结构独特和复杂的代谢物的构建中。本文综述了目前对C-C键形成自由基SAM酶的功能和机制的认识，并强调了它们在结构复杂的天然有机分子的生物合成中的重要作用。自由基SAM酶形成C-C键的机制考虑确定了三个关键机制因素的重要性：自由基起始，受体底物活化和自由基猝灭。了解这些特征酶的功能和作用机制不仅对促进我们对自由基SAM酶的认识，而且对了解天然产物和辅助因子的生物合成具有重要意义。
C–C bond formations are frequently the key steps in cofactor and natural product biosynthesis. Historically, C–C bond formations were thought to proceed by two electron mechanisms, represented by Claisen condensation in fatty acids and polyketide biosynthesis. These types of mechanisms require activated substrates to create a nucleophile and an electrophile. More recently, increasing number of C–C bond formations catalyzed by radical SAM enzymes are being identified. These free radical mediated reactions can proceed between almost any sp3 and sp2 carbon centers, allowing introduction of C–C bonds at unconventional positions in metabolites. Therefore, free radical mediated C–C bond formations are frequently found in the construction of structurally unique and complex metabolites. This review discusses our current understanding of the functions and mechanisms of C–C bond forming radical SAM enzymes and highlights their important roles in the biosynthesis of structurally complex, naturally occurring organic molecules. Mechanistic consideration of C–C bond formation by radical SAM enzymes identifies the significance of three key mechanistic factors: radical initiation, acceptor substrate activation and radical quenching. Understanding the functions and mechanisms of these characteristic enzymes will be important not only in promoting our understanding of radical SAM enzymes, but also for understanding natural product and cofactor biosynthesis.
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