Radical Breakthroughs in Natural Product and Cofactor Biosynthesis.

Radical Breakthroughs in Natural Product and Cofactor Biosynthesis.
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DOI:
10.1021/acs.biochem.7b00878
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发表时间:
2018-01-30
期刊:
影响因子:
2.9
通讯作者:
Yokoyama K
Yokoyama K
中科院分区:
生物学3区
文献类型:
--
作者:
Yokoyama K

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自由基SAM(S-腺苷-L-甲硫氨酸)超家族是最大的酶组之一,具有> 113,000个注释序列。该超家族的成员使用氧敏感的4Fe-4S簇催化SAM的还原切割,瞬时产生5 '-脱氧腺苷自由基(5'-dA·),随后用于启动多种自由基介导的反应。由于自由基的独特反应性,自由基SAM酶经常催化对辅因子和天然产物的独特结构的生物合成至关重要的化学挑战性反应。在这个角度来看,我将讨论的影响,我们的理解的生物合成途径,并使用两个最近的例子,从我自己的小组,特别强调两个自由基SAM酶负责碳骨架的形成过程中的辅因子和天然产物的生物合成。
The radical SAM (S-adenosyl-L-methionine) superfamily is one of the largest group of enzymes with >113,000 annotated sequences. Members of this superfamily catalyze the reductive cleavage of SAM using an oxygen sensitive 4Fe-4S cluster to transiently generate 5′-deoxyadenosyl radical (5′-dA•) 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 particular emphasis on two radical SAM enzymes responsible for carbon skeleton formation during the biosynthesis of a cofactor and natural products.
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