ArticleJournal of the American Chemical Society2013
Biochemical determination of enzyme-bound metabolites: preferential accumulation of a programmed octaketide on the enediyne polyketide synthase CalE8.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Biosurfactant biosynthesis by Alcanivorax borkumensis and its role in oil biodegradation.Nature chemical biology · 2025Article
- PEARL-Catalyzed Peptide Bond Formation after Chain Reversal by Ureido-Forming Condensation Domains.ACS central science · 2024Article
- Antibiotic Skeletal Diversification via Differential Enoylreductase Recruitment and Module Iteration inJournal of the American Chemical Society · 2024Article
- Dehydroamino acid residues in bioactive natural products.Natural product reports · 2024Review
- Discovery of type II polyketide synthase-like enzymes for the biosynthesis of cispentacin.Nature communications · 2023Article
- Dynemicin A Derivatives as Potential Cancer Chemotherapeutics by Mutasynthesis.Helvetica chimica acta · 2023Article
- Normal and Aberrant Methyltransferase Activities Give Insights into the Final Steps of Dynemicin A Biosynthesis.Journal of the American Chemical Society · 2023Article
- A discrete intermediate for the biosynthesis of both the enediyne core and the anthraquinone moiety of enediyne natural products.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Diene incorporation by a dehydratase domain variant in modular polyketide synthases.Nature chemical biology · 2022Article
- Discovery of pentaene polyols by the activation of an enediyne gene cluster: biosynthetic implications for 9-membered enediyne core structures.Chemical science · 2022Article
- Aminoacyl chain translocation catalysed by a type II thioesterase domain in an unusual non-ribosomal peptide synthetase.Nature communications · 2022Article
- A metabolic regulon reveals early and late acting enzymes in neuroactive Lycopodium alkaloid biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Acyl Donor Stringency and Dehydroaminoacyl Intermediates in β-Lactam Formation by a Non-ribosomal Peptide Synthetase.ACS chemical biology · 2021Article
- In vivo and in vitro reconstitution of unique key steps in cystobactamid antibiotic biosynthesis.Nature communications · 2021Article
- C-N-Coupled Metabolites Yield Insights into Dynemicin A Biosynthesis.Chembiochem : a European journal of chemical biology · 2020Article
- Characterization of Acyl Carrier Protein-Dependent Glycosyltransferase in Mitomycin C Biosynthesis.Biochemistry · 2019Article
- Mechanism of Integrated β-Lactam Formation by a Nonribosomal Peptide Synthetase during Antibiotic Synthesis.Biochemistry · 2018Article
- In Vitro Biosynthesis of the Nonproteinogenic Amino Acid Methoxyvinylglycine.Angewandte Chemie (International ed. in English) · 2018Article
- Characterization of an Anthracene Intermediate in Dynemicin Biosynthesis.Angewandte Chemie (International ed. in English) · 2018Article
- A dual role for a polyketide synthase in dynemicin enediyne and anthraquinone biosynthesis.Nature chemistry · 2018Article
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Abstract
Despite considerable interest in the enediyne family of antitumor antibiotics, assembly of their polyketide core structures in nature remains poorly understood. Discriminating methods to access enzyme-bound intermediates are critical for elucidating unresolved polyketide and nonribosomal peptide biosynthetic pathways. Here, we describe the development of broadly applicable techniques for the mild chemical release and analysis of intermediates bound to carrier proteins (CPs), providing access to these species even in sensitive systems. These techniques were applied to CalE8, the polyketide synthase (PKS) involved in calicheamicin biosynthesis, facilitating the unambiguous identification of enzyme-bound polyketides on an enediyne PKS. Moreover, these methods enabled the preparation of fully unloaded CalE8, providing a "clean slate" for reconstituted activity and allowing us to demonstrate the preferential accumulation of a PKS-bound octaketide with evidence of programmed processing control by CalE8. This intermediate, which has the expected chain length for enediyne core construction, could previously only be indirectly inferred. These studies prove that this polyketide is an authentic product of CalE8 and may be a key precursor to the enediyne core of calicheamicin, as it is the only programmed, enzyme-bound species observed for any enediyne system to date. Our experimental advances into a generally inaccessible system illustrate the utility of these techniques for investigating CP-based biosynthetic pathways.
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