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A Lanthipeptide‐like N‐Terminal Leader Region Guides Peptide Epimerization by Radical SAM Epimerases: Implications for RiPP Evolution
Author(s) -
Fuchs Sebastian W.,
Lackner Gerald,
Morinaka Brandon I.,
Morishita Yohei,
Asai Teigo,
Riniker Sereina,
Piel Jörn
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201602863
Subject(s) - epimer , peptide , stereochemistry , biosynthesis , chemistry , enzyme , biology , biochemistry
Ribosomally synthesized and posttranslationally modified peptide natural products (RiPPs) exhibit diverse structures and bioactivities and are classified into distinct biosynthetic families. A recently reported family is the proteusins, with the prototype members polytheonamides being generated by almost 50 maturation steps, including introduction of d ‐residues at multiple positions by an unusual radical SAM epimerase. A region in the protein‐like N‐terminal leader of proteusin precursors is identified that is crucial for epimerization. It resembles a precursor motif previously shown to mediate interaction in thioether bridge‐formation in class I lanthipeptide biosynthesis. Beyond this region, similarities were identified between proteusin and further RiPP families, including class I lanthipeptides. The data suggest that common leader features guide distinct maturation types and that nitrile hydratase‐like enzymes are ancestors of several RiPP classes.