Macrocyclization via an Arginine-Tyrosine Crosslink Broadens the Reaction Scope of Radical -Adenosylmethionine Enzymes.

Publication Year
2019

Type

Journal Article
Abstract

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.

Journal
J Am Chem Soc
Volume
141
Issue
42
Pages
16610-16614
Date Published
2019 Oct 23
ISSN Number
1520-5126
Alternate Journal
J Am Chem Soc
PMID
31596076