title: Identification and Structural Characterization of Naturally-Occurring Broad-Spectrum Cyclic Antibiotics Isolated from Paenibacillus.
abstract: The rise of antimicrobial resistance necessitates the discovery and/or production of novel antibiotics. Isolated strains of Paenibacillus alvei were previously shown to exhibit antimicrobial activity against a number of pathogens, such as E. coli, Salmonella, and methicillin-resistant Staphylococcus aureus (MRSA). The responsible antimicrobial compounds were isolated from these Paenibacillus strains and a combination of low and high resolution mass spectrometry with multiple-stage tandem mass spectrometry was used for identification. A group of closely related cyclic lipopeptides was identified, differing primarily by fatty acid chain length and one of two possible amino acid substitutions. Variation in the fatty acid length resulted in mass differences of 14 Da and yielded groups of related MS(n) spectra. Despite the inherent complexity of MS/MS spectra of cyclic compounds, straightforward analysis of these spectra was accomplished by determining differences in complementary product ion series between compounds that differ in molecular weight by 14 Da. The primary peptide sequence assignment was confirmed through genome mining; the combination of these analytical tools represents a workflow that can be used for the identification of complex antibiotics. The compounds also share amino acid sequence similarity to a previously identified broad-spectrum antibiotic isolated from Paenibacillus. The presence of such a wide distribution of related compounds produced by the same organism represents a novel class of broad-spectrum antibiotic compounds.
authors.affiliation: U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, HFS-707, 5100 Paint Branch Pkwy, College Park, MD, 20740, USA. Ann.Knolhoff@fda.hhs.gov.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Knolhoff
authors.affiliation: U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, HFS-707, 5100 Paint Branch Pkwy, College Park, MD, 20740, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, HFS-707, 5100 Paint Branch Pkwy, College Park, MD, 20740, USA.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: McFarland
authors.affiliation: U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, HFS-707, 5100 Paint Branch Pkwy, College Park, MD, 20740, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, HFS-707, 5100 Paint Branch Pkwy, College Park, MD, 20740, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Callahan
authors.affiliation: U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, HFS-707, 5100 Paint Branch Pkwy, College Park, MD, 20740, USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Brown
authors.affiliation: U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, HFS-707, 5100 Paint Branch Pkwy, College Park, MD, 20740, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Croley
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008969:Molecular Sequence Data; D056507:Paenibacillus / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic
keywords: Antibiotic; Bacteria; Cyclic lipopeptides; Cyclic peptide; Identification; Mass spectrometry; Non-ribosomal peptide; Paenibacillus