Food-poisoning bacteria employ a citrate synthase and a type II NRPS to synthesize bolaamphiphilic lipopeptide antibiotics.
(2020) Food-poisoning bacteria employ a citrate synthase and a type II NRPS to synthesize bolaamphiphilic lipopeptide antibiotics. Angew Chem Int Ed [Epub ahead of print]
Mining the genome of the food-spoiling bacterium Burkholderia gladioli pv. cocovenenans revealed five non-ribosomal peptide synthetase (NRPS) gene clusters, including an orphan gene locus ( bol ). Gene inactivation and metabolic profiling linked the bol gene cluster to novel bolaamphiphilic lipopeptides with antimycobacterial activity. A combination of chemical analyses and bioinformatics elucidated the structures of bolagladin A and B, lipocyclopeptides featuring an unusual dehydro-β-alanine enamide linker fused to an unprecedented tricarboxylic fatty acid tail. Through a series of targeted gene deletions we proved the involvement of a designated citrate synthase (CS), priming ketosynthases (KS III), a type II NRPS including a novel desaturase for enamide formation, and a multimodular NRPS generating the cyclopeptide. Network analyses revealed the evolutionary origin of the CS and identified cryptic CS/NRPS gene loci in various bacterial genomes.
doi: 10.1002/anie.202009107 PMID: 32780428