title: Involvement and unusual substrate specificity of a prolyl oligopeptidase in class III lanthipeptide maturation.
abstract: Lanthipeptides represent an important group of ribosomally synthesized and post-translationally modified peptides (RiPPs). Commonly, in the last steps of their maturation, a part of the peptide, termed the leader, is removed, providing the active compound. This contribution describes for the first time the identification of a protease involved in the removal of the leader peptide of a class III lanthipeptide. Four putative class III biosynthetic gene clusters were identified in bacterial genomes, each containing a gene encoding a prolyl oligopeptidase (POP). Further in vitro investigations of the gene cluster from Kribbella flavida , involving reconstitution of the biosynthesis of the new lanthipeptide flavipeptin, proved that a POP-type FlaP protease is responsible for leader removal. Interestingly, detailed in vitro studies of the substrate specificity revealed that FlaP is specific to the post-translationally modified peptide and can discriminate between N- and C-terminal rings. Therefore, it has been shown for the first time that factors other than size and amino acid sequence might be involved in substrate recognition by POPs.
authors: Institut für Chemie, Technische Universität Berlin, Strasse des 17 Juni 124, 10623 Berlin, Germany.
authors: Ginka H
authors: GH
authors: Völler
authors: Bartlomiej
authors: B
authors: Krawczyk
authors: Paul
authors: P
authors: Ensle
authors: Roderich D
authors: RD
authors: Süssmuth
mesh_terms: D008968:Molecular Conformation; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D010455:Peptides; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases