Atropopeptides are a Novel Family of Ribosomally Synthesized and Posttranslationally Modified Peptides with a Complex Molecular Shape.

ABSTRACT: Biomacromolecules are known to feature complex three-dimensional shapes that are essential for their function. Among natural products, ambiguous molecular shapes are a rare phenomenon. The hexapeptide tryptorubin A can adopt one of two unusual atropisomeric configurations. Initially hypothesized to be a non-ribosomal peptide, we show that tryptorubin A is the first characterized member of a new family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) that we named atropopeptides. The sole modifying enzyme encoded in the gene cluster, a cytochrome P450 monooxygenase, is responsible for the atropospecific formation of one carbon-carbon and two carbon-nitrogen bonds. The characterization of two additional atropopeptide biosynthetic pathways revealed a two-step maturation process. Atropopeptides promote pro-angiogenic cell functions as indicated by an increase in endothelial cell proliferation and undirected migration. Our study expands the biochemical space of RiPP-modifying enzymes and paves the way towards the chemoenzymatic utilization of atropopeptide-modifying P450s.

SUBMITTER: Nanudorn P 

PROVIDER: S-EPMC9826248 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature