title: Paenibacillus polymyxa PKB1 produces variants of polymyxin B-type antibiotics.
abstract: Polymyxins are cationic lipopeptide antibiotics active against many species of Gram-negative bacteria. We sequenced the gene cluster for polymyxin biosynthesis from Paenibacillus polymyxa PKB1. The 40.8 kb gene cluster comprises three nonribosomal peptide synthetase-encoding genes and two ABC transporter-like genes. Disruption of a peptide synthetase gene abolished all antibiotic production, whereas deletion of one or both transporter genes only reduced antibiotic production. Computational analysis of the peptide synthetase modules suggested that the enzyme system produces variant forms of polymyxin B (1 and 2), with D-2,4-diaminobutyrate instead of L-2,4-diaminobutyrate in amino acid position 3. Two antibacterial metabolites were resolved by HPLC and identified by high-resolution mass spectrometry and MS/MS sequencing as the expected variants 3 and 4 of polymyxin B(1) (1) and B(2) (2). Stereochemical analysis confirmed the presence of both D-2,4-diaminobutyrate and L-2,4-diaminobutyrate residues.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shaheen
authors.forename: Jingru
authors.initials: J
authors.lastname: Li
authors.forename: Avena C
authors.initials: AC
authors.lastname: Ross
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
authors.forename: Susan E
authors.initials: SE
authors.lastname: Jensen
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D008969:Molecular Sequence Data; D005810:Multigene Family; D056507:Paenibacillus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011113:Polymyxins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins; C571510:polymyxin B2; C121746:polymyxin B(1); D010453:Peptide Synthases