ArticleJournal of the American Chemical Society2017
Chemoenzymatic Total Synthesis and Structural Diversification of Tylactone-Based Macrolide Antibiotics through Late-Stage Polyketide Assembly, Tailoring, and C-H Functionalization.
Article in Journal of the American Chemical Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential.Chembiochem : a European journal of chemical biology · 2026Review
- Development of Keystone Macrolide Antibiotics via Selective Oxidation.ACS central science · 2026Article
- Article
- Discovery of a New Rosamicin Derivative from EndophyticMolecules (Basel, Switzerland) · 2026Article
- Establishing Selectivity Trends with Reactions of Thioesterases and Semi-Synthetic Polyketides.Journal of the American Chemical Society · 2025Article
- Chemoenzymatic Skeletal Editing of Natural Product Scaffolds via P450-Controlled Site-Selective Ring Expansion at Aliphatic C─H Sites.Angewandte Chemie (International ed. in English) · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Directed Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System.ACS catalysis · 2025Article
- Article
- Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products.Natural product reports · 2024Review
- Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation.ACS catalysis · 2024Article
- Structure-Activity Relationships of Natural and Semisynthetic Plecomacrolides Suggest Distinct Pathways for HIV-1 Immune Evasion and Vacuolar ATPase-Dependent Lysosomal Acidification.Journal of medicinal chemistry · 2024Article
- Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization.Beilstein journal of organic chemistry · 2024Review
- Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations.Beilstein journal of organic chemistry · 2024Review
- Recent Developments and Applications of Biocatalytic and Chemoenzymatic Synthesis for the Generation of Diverse Classes of Drugs.Current pharmaceutical biotechnology · 2024Article
- Current State-of-the-Art Toward Chemoenzymatic Synthesis of Polyketide Natural Products.Chembiochem : a European journal of chemical biology · 2023Review
- Electrochemical Late-Stage Functionalization.Chemical reviews · 2023Review
- Structure of a modular polyketide synthase reducing region.Structure (London, England : 1993) · 2023Article
- Review
- 1,3-Diamine-Derived Catalysts: Design, Synthesis, and the Use in Enantioselective Mannich Reactions of Ketones.The Journal of organic chemistry · 2023Article
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Authors and funding
12 authors.
Funding
Abstract
Polyketide synthases (PKSs) represent a powerful catalytic platform capable of effecting multiple carbon-carbon bond forming reactions and oxidation state adjustments. We explored the functionality of two terminal PKS modules that produce the 16-membered tylosin macrocycle, using them as biocatalysts in the chemoenzymatic synthesis of tylactone and its subsequent elaboration to complete the first total synthesis of the juvenimicin, M-4365, and rosamicin classes of macrolide antibiotics via late-stage diversification. Synthetic chemistry was employed to generate the tylactone hexaketide chain elongation intermediate that was accepted by the juvenimicin (Juv) ketosynthase of the penultimate JuvEIV PKS module. The hexaketide is processed through two complete modules (JuvEIV and JuvEV) in vitro, which catalyze elongation and functionalization of two ketide units followed by cyclization of the resulting octaketide into tylactone. After macrolactonization, a combination of in vivo glycosylation, selective in vitro cytochrome P450-mediated oxidation, and chemical oxidation was used to complete the scalable construction of a series of macrolide natural products in as few as 15 linear steps (21 total) with an overall yield of 4.6%.
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