ArticleNature chemistry2019
A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Natural products shape microbial ecology and disease in the cystic fibrosis airway.Natural product reports · 2026Review
- Condensation-independent intramodular translocation mechanism of the trans-AT polyketide synthase assembly line.Nature chemical biology · 2026Article
- Molecular basis for depsipeptide HDAC inhibitor combinatorial biosynthesis.Nature communications · 2026Article
- Article
- Divergent Tandem Acyl Carrier Proteins Necessitate In-Series Polyketide Processing in the Leinamycin Family.Angewandte Chemie (International ed. in English) · 2025Article
- Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins.Science (New York, N.Y.) · 2024Article
- Giant polyketide synthase enzymes biosynthesize a giant marine polyether biotoxin.bioRxiv : the preprint server for biology · 2024Article
- Plant and marine-derived natural products: sustainable pathways for future drug discovery and therapeutic development.Frontiers in pharmacology · 2024Review
- Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.Nature reviews. Drug discovery · 2023Review
- No job too small for a giant enzyme.Nature chemical biology · 2023Article
- Decrypting the programming of β-methylation in virginiamycin M biosynthesis.Nature communications · 2023Article
- Cloning and expression of Burkholderia polyyne biosynthetic gene clusters in Paraburkholderia hosts provides a strategy for biopesticide development.Microbial biotechnology · 2022Article
- Enzymatic assembly of the salinosporamide γ-lactam-β-lactone anticancer warhead.Nature chemical biology · 2022Article
- Biosynthesis of triacsin featuring an N-hydroxytriazene pharmacophore.Nature chemical biology · 2021Article
- Natural products in drug discovery: advances and opportunities.Nature reviews. Drug discovery · 2021Review
- Biosynthesis of Chlorinated Lactylates inJournal of natural products · 2021Article
- Genomic Assemblies of Members ofMicrobiology resource announcements · 2020Article
- Fungal siderophore biosynthesis catalysed by an iterative nonribosomal peptide synthetase.Chemical science · 2020Article
- A rapid screening method for the detection of specialised metabolites from bacteria: Induction and suppression of metabolites from Burkholderia species.Journal of microbiological methods · 2020Article
- Structural basis for chain release from the enacyloxin polyketide synthase.Nature chemistry · 2019Article
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Authors and funding
10 authors.
Funding
Abstract
Polyketide synthases assemble diverse natural products with numerous important applications. The thioester intermediates in polyketide assembly are covalently tethered to acyl carrier protein domains of the synthase. Several mechanisms for polyketide chain release are known, contributing to natural product structural diversification. Here, we report a dual transacylation mechanism for chain release from the enacyloxin polyketide synthase, which assembles an antibiotic with promising activity against Acinetobacter baumannii. A non-elongating ketosynthase domain transfers the polyketide chain from the final acyl carrier protein domain of the synthase to a separate carrier protein, and a non-ribosomal peptide synthetase condensation domain condenses it with (1S,3R,4S)-3,4-dihydroxycyclohexane carboxylic acid. Molecular dissection of this process reveals that non-elongating ketosynthase domain-mediated transacylation circumvents the inability of the condensation domain to recognize the acyl carrier protein domain. Several 3,4-dihydroxycyclohexane carboxylic acid analogues can be employed for chain release, suggesting a promising strategy for producing enacyloxin analogues.
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