title: Peptide macrocyclization: the reductase of the nostocyclopeptide synthetase triggers the self-assembly of a macrocyclic imine.
abstract: Many biologically active natural products have macrocyclic structures. In nonribosomal peptides macrocyclization is commonly achieved via the formation of intramolecular ester or amide bond catalyzed by thioesterase domains during biosynthesis. A unique and so far unknown type of peptide cyclization occurs in the nostocyclopeptide, a macrocyclic imine produced by the terrestrial cyanobacterium Nostoc sp. ATCC53789. In this work we show that a C-terminal reductase domain of the nostocyclopeptide nonribosomal peptide synthetase catalyzes the reductive release of a linear peptide aldehyde and thereby triggers the spontaneous formation of a stable imino head-to-tail linkage. This type of molecular self-assembly induced by the reductive release of reactive aldehydes may be more commonplace in other complex nonribosomal peptides than originally thought.
authors.affiliation: Fachbereich Chemie/Biochemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35043 Marburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kopp
authors.forename: Christoph
authors.initials: C
authors.lastname: Mahlert
authors.forename: Jan
authors.initials: J
authors.lastname: Grünewald
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Marahiel
mesh_terms: D003500:Cyclization; D007097:Imines / Q000737:chemistry*; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry*; D010453:Peptide Synthases / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D007097:Imines; D009842:Oligopeptides; D010456:Peptides, Cyclic; C428166:nostocyclopeptide A1; C428167:nostocyclopeptide A2; D010088:Oxidoreductases; D010453:Peptide Synthases