title: Structural characterization of the highly cyclized lantibiotic paenicidin A via a partial desulfurization/reduction strategy.
abstract: Lantibiotics are ribosomally synthesized antimicrobial peptides produced by bacteria that are increasingly of interest for food preservation and possible therapeutic uses. These peptides are extensively post-translationally modified, and are characterized by lanthionine and methyllanthionine thioether cross-links. Paenibacillus polymyxa NRRL B-30509 was found to produce polymyxins and tridecaptins, in addition to a novel lantibiotic termed paenicidin A. A bacteriocin termed SRCAM 602 previously reported to be produced by this organism and claimed to be responsible for inhibition of Campylobacter jejuni could not be detected either directly or by genomic analysis. The connectivities of the thioether cross-links of paenicidin A were solved using a novel partial desulfurization/reduction strategy in combination with tandem mass spectrometry. This approach overcame the limitations of NMR-based structural characterization that proved mostly unsuccessful for this peptide. Paenicidin A is a highly cyclized lantibiotic, containing six lanthionine and methyllanthionine rings, three of which are interlocking.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Lohans
authors.forename: Zedu
authors.initials: Z
authors.lastname: Huang
authors.forename: Marco J
authors.initials: MJ
authors.lastname: van Belkum
authors.forename: Maude
authors.initials: M
authors.lastname: Giroud
authors.forename: Clarissa S
authors.initials: CS
authors.lastname: Sit
authors.forename: Erika M
authors.initials: EM
authors.lastname: Steels
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Randy M
authors.initials: RM
authors.lastname: Whittal
authors.forename: Lynn M
authors.initials: LM
authors.lastname: McMullen
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D001430:Bacteriocins / Q000737:chemistry*; D003500:Cyclization; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D056507:Paenibacillus / Q000201:enzymology / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C581110:paenicidin A; D013455:Sulfur