Macrocyclization via an Arginine-Tyrosine Crosslink Broadens the Reaction Scope of Radical -Adenosylmethionine Enzymes. Author Alessio Caruso, Ryan Martinie, Leah Bushin, Mohammad Seyedsayamdost 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. Keywords S-Adenosylmethionine, Amino Acid Sequence, Enzymes, Arginine, Tyrosine, Streptococcus suis, Cyclization Journal J Am Chem Soc Volume 141 Issue 42 Pages 16610-16614 Date Published 2019 Oct 23 ISSN Number 1520-5126 DOI 10.1021/jacs.9b09210 Alternate Journal J Am Chem Soc PMID 31596076 PubMedGoogle ScholarBibTeXEndNote X3 XML