Department of Chemistry , Princeton University , Princeton , New Jersey 08544 , United States.
Department of Molecular Biology , Princeton University , Princeton , New Jersey 08544 , United States.
J Am Chem Soc. 2019 Oct 23;141(42):16610-16614. doi: 10.1021/jacs.9b09210. Epub 2019 Oct 14.
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 -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 δ-carbon of an arginine side chain to the -position 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.
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，我们鉴定了大量受群体感应调控的 RiPP 基因簇，这些基因簇编码一种或多种自由基 -腺苷甲硫氨酸（RaS）酶，这是一个能够催化化学转化的多样化蛋白质超家族。在这项工作中，我们描述了一种由 RaS 酶的一个亚家族在 RiPP 生物合成过程中催化的新反应：在精氨酸侧链的非活性 δ-碳原子与酪氨酸-苯酚的 - 位之间形成一个大环碳-碳键。此外，我们表明，与 RiPP 生物合成的通常情况不同，该转化对前体肽的引导部分的干扰基本不敏感。该反应扩展了 RaS 酶的作用范围，并为不断增加的 RiPP 结构提供了一个独特的环化模体。
