Discovery and Biosynthesis of Bolagladins: Unusual Lipodepsipeptides from Burkholderia gladioli Clinical Isolates

Yousef Dashti, Ioanna T. Nakou, Alex J. Mullins, Gordon Webster, Xinyun Jian, Eshwar Mahenthiralingam, Gregory L. Challis

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Two Burkholderia gladioli strains isolated from the lungs of cystic fibrosis patients were found to produce unusual lipodepsipeptides containing a unique citrate-derived fatty acid and a rare dehydro-β-alanine residue. The gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis. In-frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster, which was found in the genomes of about 45 % of B. gladioli isolates, suggesting that its metabolic products play an important role in the growth and/or survival of the species. The Chrome Azurol S assay indicated that these metabolites bind ferric iron, which suppresses their production when added to the growth medium. Moreover, a gene encoding a TonB-dependent ferric-siderophore receptor is adjacent to the biosynthetic genes, suggesting that these metabolites may function as siderophores in B. gladioli.

Original languageEnglish
Number of pages10
JournalAngewandte Chemie - International Edition
DOIs
Publication statusAccepted/In press - 11 Aug 2020

Keywords

  • biosynthesis
  • fatty acids
  • genome mining
  • natural products
  • nonribosomal peptide synthetase

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