Characterization of the gene cluster encoding a non-ribosomal peptide synthetase for polymyxin biosynthesis in Paenibacillus polymyxa PKB1

• Author / Creator

  Shaheen, Md.

• Polymyxins are cationic lipopeptide antibiotics, and are considered to be drugs of last resort to fight against multidrug resistant Gram negative bacteria. In this study the gene cluster encoding the non-ribosomal peptide synthetase which catalyses polymyxin biosynthesis was identified and sequenced in Paenibacillus polymyxa PKB1. The gene cluster consists of three biosynthetic genes and two ABC transporter-like genes. Disruption of a biosynthetic gene resulted in complete loss of antibiotic production whereas deletion of one or both transporter genes resulted in reduced antibiotic production. Two antibacterial compounds were identified in the wild type culture supernatants by HPLC analysis and agar diffusion bioassay. LC-MS and bioinformatic analysis suggested these compounds to be analogs of polymyxin B2 and B1, containing a D-DAB instead of L-DAB residue in position three of the molecules.

• Subjects / Keywords

  • 2, 4 diamino butyric acid
  • Polymyxin
  • Non-ribosomal peptide synthetase

• Graduation date

  Spring 2011

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3Z12N

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.