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Publication Abstract from PubMed

Graspetides, also known as omega-ester-containing peptides (OEPs), are a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) bearing side chain-to-side chain macrolactone or macrolactam linkages. Here, we present the molecular details of precursor peptide recognition by the macrocyclase enzyme PsnB in the biosynthesis of plesiocin, a group 2 graspetide. Biochemical analysis revealed that, in contrast to other RiPPs, the core region of the plesiocin precursor peptide noticeably enhanced the enzyme-precursor interaction via the conserved glutamate residues. We obtained four crystal structures of symmetric or asymmetric PsnB dimers, including those with a bound core peptide and a nucleotide, and suggest that the highly conserved Arg213 at the enzyme active site specifically recognizes a ring-forming acidic residue before phosphorylation. Collectively, this study provides insights into the mechanism underlying substrate recognition in graspetide biosynthesis and lays a foundation for engineering new variants.

Molecular mechanism underlying substrate recognition of the peptide macrocyclase PsnB.,Song I, Kim Y, Yu J, Go SY, Lee HG, Song WJ, Kim S Nat Chem Biol. 2021 Nov;17(11):1123-1131. doi: 10.1038/s41589-021-00855-x. Epub , 2021 Sep 2. PMID:34475564^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.