Macrocyclization via an Arginine-Tyrosine Crosslink Broadens the Reaction Scope of Radical S-Adenosylmethionine Enzymes
Macrocyclization via an Arginine-Tyrosine Crosslink Broadens the Reaction Scope of Radical S-Adenosylmethionine Enzymes
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DOI：
10.1021/jacs.9b09210
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发表时间：
2019-10-23
影响因子：
15
通讯作者：
Seyedsayamdost, Mohammad R.
中科院分区：
文献类型：
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作者：
Caruso, Alessio;Martinie, Ryan J.;Seyedsayamdost, Mohammad R.
核糖体合成和翻译后修饰肽（RiPPs）是一类具有多种结构和功能的新兴天然产物。最近，我们发现了一系列广泛的RiPP基因簇，这些基因簇受群体感应调节，编码一个或多个自由基s -腺苷蛋氨酸（RaS）酶，这是一个多样化的蛋白质超家族，能够催化化学上困难的转化。在这项工作中，我们描述了在RiPP生物合成过程中由一个这样的RaS酶亚家族催化的一种新反应：安装一个大环碳-碳键，将精氨酸侧链的未活化δ碳连接到酪氨酸-苯酚的正位。此外，我们表明，这种转化是不寻常的RiPP生物发生，在很大程度上对前体肽前导部分的扰动不敏感。该反应扩大了RaS酶的范围，并为RiPP结构的不断发展提供了独特的大环化基序。
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an ascendant class of natural products with diverse structures and functions. Recently, we identified a wide array of RiPP gene clusters that are regulated by quorum sensing and encode one or more radical S-adenosylmethionine (RaS) enzymes, a diverse protein superfamily capable of catalyzing chemically difficult transformations. In this work, we characterize a novel reaction catalyzed by one such subfamily of RaS enzymes during RiPP biosynthesis: installation of a macrocyclic carbon-carbon bond that links the unactivated delta-carbon of an arginine side chain to the orthoposition of a tyrosine-phenol. Moreover, we show that this transformation is, unusually for RiPP biogenesis, largely insensitive to perturbations of the leader portion of the precursor peptide. This reaction expands the already impressive scope of RaS enzymes and contributes a unique macrocyclization motif to the growing body of RiPP architectures.