title: Dissecting reactions of nonlinear precursor peptide processing of the class III lanthipeptide curvopeptin.
abstract: Lanthipeptides are ribosomally synthesized peptides which undergo extensive post-translational modifications. In addition to novel structural features and bioactivities, the in vitro study on the biosynthesis of the class III lanthipeptide labyrinthopeptin revealed a unique C- to N-terminal directionality of biosynthetic processing. The recently described class III lanthipeptide curvopeptin allowed investigating the directionality aspect in much greater detail: Structural characterization of nine curvopeptin biosynthesis intermediates by high-resolution mass spectrometry combined with a deuterium-labeling approach enabled for the first time building a comprehensive biosynthesis model featuring all three post-translational modification reactions: phosphorylation, elimination, and cyclization. These results point to a nonlinear processing scheme with a predominant C → N-terminal directionality. Our data give important mechanistic insights into the concerted processing and directionality of the multifunctional class III modifying enzymes. The data are of significance in the light of obtaining a mechanistic understanding of the post-translational biosynthesis machinery of the growing variety of ribosomally synthesized and post-translationally modified peptides.
authors.affiliation: Fakultät II-Institut für Chemie, Technische Universität Berlin , Strasse des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Jungmann
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Krawczyk
authors.forename: Marcel
authors.initials: M
authors.lastname: Tietzmann
authors.forename: Paul
authors.initials: P
authors.lastname: Ensle
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
mesh_terms: D000595:Amino Acid Sequence; D003500:Cyclization; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012270:Ribosomes / Q000378:metabolism
chemical_list: D010455:Peptides