Food-Poisoning Bacteria Employ a Citrate Synthase and a Type II NRPS To Synthesize Bolaamphiphilic Lipopeptide Antibiotics*.
biosynthesis
fatty acids
genome mining
lipopeptides
nonribosomal peptides
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
23 11 2020
23 11 2020
Historique:
received:
01
07
2020
pubmed:
12
8
2020
medline:
20
3
2021
entrez:
12
8
2020
Statut:
ppublish
Résumé
Mining the genome of the food-spoiling bacterium Burkholderia gladioli pv. cocovenenans revealed five nonribosomal 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 analysis 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 III (KS III), a type II NRPS, including a novel desaturase for enamide formation, and a multimodular NRPS in generating the cyclopeptide. Network analyses revealed the evolutionary origin of the CS and identified cryptic CS/NRPS gene loci in various bacterial genomes.
Identifiants
pubmed: 32780428
doi: 10.1002/anie.202009107
pmc: PMC7756705
doi:
Substances chimiques
Anti-Bacterial Agents
0
Lipopeptides
0
Citrate (si)-Synthase
EC 2.3.3.1
Peptide Synthases
EC 6.3.2.-
non-ribosomal peptide synthase
EC 6.3.2.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21535-21540Informations de copyright
© 2020 The Authors. Published by Wiley-VCH GmbH.
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