title: A Lanthipeptide-like N-Terminal Leader Region Guides Peptide Epimerization by Radical SAM Epimerases: Implications for RiPP Evolution.
abstract: 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.
authors: Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
authors: Sebastian W
authors: SW
authors: Fuchs
authors: Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
authors: Gerald
authors: G
authors: Lackner
authors: Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
authors: Brandon I
authors: BI
authors: Morinaka
authors: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aobaku, Sendai, Japan.
authors: Yohei
authors: Y
authors: Morishita
authors: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aobaku, Sendai, Japan.
authors: Teigo
authors: T
authors: Asai
authors: Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093, Zurich, Switzerland.
authors: Sereina
authors: S
authors: Riniker
authors: Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland. jpiel@ethz.ch.
authors: Jörn
authors: 0000-0002-2282-8154
authors: J
authors: Piel
keywords: RiPPs; epimerases; lanthipeptides; leader peptides; proteusin