Structural Characterization of the Highly Cyclized Lantibiotic Paenicidin A via a Partial Desulfurization/Reduction Strategy

• Published in: Journal of the American Chemical Society Vol. 134; no. 48; pp. 19540 - 19543
• Main Authors: Lohans, Christopher T, Huang, Zedu, van Belkum, Marco J, Giroud, Maude, Sit, Clarissa S, Steels, Erika M, Zheng, Jing, Whittal, Randy M, McMullen, Lynn M, Vederas, John C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 05-12-2012
• Subjects: Amino Acid Sequence; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; Bacteriocins - chemistry; Cyclization; Molecular Sequence Data; Oxidation-Reduction; Paenibacillus - enzymology; Paenibacillus - metabolism; Sulfur - chemistry; Tandem Mass Spectrometry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja3089229

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.