Polyketide biosynthesis is the enzymatic assembly of carbon skeletons from short-chain acyl precursors through repeated carbon–carbon bond formation [1]. Polyketide synthases select starter and extender units and catalyze decarboxylative condensations; optional processing of the resulting intermediates establishes their oxidation states and substitution patterns [2]. Modular assembly lines can terminate chains through cyclization, while additional tailoring enzymes modify the initially assembled scaffold through oxidation, ring formation, or other reactions [3]. Carrier-protein domains tether intermediates through a phosphopantetheine-linked thioester and deliver them to successive catalytic domains. Domain recognition and movement coordinate extension and modification within the enzyme system. The order of these reactions, together with precursor selection and chain-release chemistry, specifies the structural framework of the resulting polyketide [4][5].
- polyketide synthase
- chain elongation
- acyl carrier protein
- natural products
Microbial Natural Products and Biosynthesis·Pharmacology·Medicine·Health Sciences
References
- Jordan L. Meier; Michael D. Burkart; The Chemical Biology of Modular Biosynthetic Enzymes. Chem. Soc. Rev. 2009, 38, 2012-2045, 10.1039/b805115c.
- Stefano Donadio; Michael J. Staver; James B. McAlpine; Susan J. Swanson; Leonard Katz; Modular Organization of Genes Required for Complex Polyketide Biosynthesis. Science 1991, 252, 675-679, 10.1126/science.2024119.
- Chaitan Khosla; Rajesh S. Gokhale; John R. Jacobsen; David E. Cane; Tolerance and Specificity of Polyketide Synthases. Annu. Rev. Biochem. 1999, 68, 219-253, 10.1146/annurev.biochem.68.1.219.
- Kira J. Weissman; Decision Making by Modular Polyketide Synthases and Implications for Genetic Engineering. Nat. Prod. Rep. 2026, 43, 961-1007, 10.1039/d6np00010j.
- Jordan L. Meier; Michael D. Burkart; The Chemical Biology of Modular Biosynthetic Enzymes. Chem. Soc. Rev. 2009, 38, 2012-2045, 10.1039/b805115c.