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Discovery and Biosynthesis of Bolagladins: Unusual Lipodepsipeptides from Burkholderia gladioli Clinical Isolates**
Authors:Dr. Yousef Dashti  Ioanna T. Nakou  Dr. Alex J. Mullins  Dr. Gordon Webster  Dr. Xinyun Jian  Prof. Eshwar Mahenthiralingam  Prof. Gregory L. Challis
Affiliation:1. Department of Chemistry, University of Warwick, Coventry, CV4 7AL UK;2. Microbiomes, Microbes and Informatics Group, Organisms and Environment Division, School of Biosciences, Cardiff University, Cardiff, CF103 AT UK;3. Department of Chemistry, University of Warwick, Coventry, CV4 7AL UK

Warwick Integrative Synthetic Biology Centre, University of Warwick, Coventry, CV4 7AL UK

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.
Keywords:biosynthesis  fatty acids  genome mining  natural products  nonribosomal peptide synthetase
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