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Paenibacillus polymyxa PKB1 produces variants of polymyxin B-type antibiotics

Mohamed Shaheen1, Jingru Li, Avena C Ross

  • 1Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.

Chemistry & Biology
|December 27, 2011
PubMed

Insights

Researchers sequenced the polymyxin biosynthesis gene cluster in Paenibacillus polymyxa PKB1. This revealed the genetic basis for producing polymyxin variants, including those with D-2,4-diaminobutyrate.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Polymyxins are crucial cationic lipopeptide antibiotics effective against Gram-negative bacteria.
  • Understanding polymyxin biosynthesis is vital for developing new antimicrobial strategies.

Purpose of the Study:

  • To sequence and analyze the gene cluster responsible for polymyxin biosynthesis in Paenibacillus polymyxa PKB1.
  • To elucidate the genetic basis for polymyxin variant production.

Main Methods:

  • Gene sequencing of the polymyxin biosynthesis cluster.
  • Gene disruption and deletion experiments.
  • High-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) for metabolite identification.
  • MS/MS sequencing and stereochemical analysis.

Main Results:

  • A 40.8 kb gene cluster containing three nonribosomal peptide synthetase (NRPS) genes and two ABC transporter genes was identified.
  • Disruption of an NRPS gene completely halted antibiotic production.
  • Deletion of transporter genes partially reduced antibiotic production.
  • Two polymyxin B variants, differing in amino acid position 3 (D-2,4-diaminobutyrate), were identified and confirmed.

Conclusions:

  • The sequenced gene cluster encodes the biosynthesis of polymyxins in P. polymyxa PKB1.
  • The NRPS genes are essential for polymyxin production, while transporter genes modulate it.
  • The study identified novel polymyxin variants, expanding the known polymyxin structural diversity.

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