Polyketide

Polyketides are a large group of secondary metabolites which either contain alternating carbonyl groups and methylene groups (-CO-CH2-), or are derived from precursors which contain such alternating groups.[1] Many polyketides are medicinal or exhibit acute toxicity.

BiosynthesisEdit

Polyketides are produced in bacteria, fungi, plants, and certain marine animals. The biosynthesis involves stepwise condensation of acetyl-CoA or propionyl-CoA with either malonyl-CoA or methylmalonyl-CoA. The condensation reaction is accompanied by the decarboxylation of the extender unit and yields a beta-keto functional group. The first condensation yields an acetoacetyl group, a diketide. Subsequent condensatiions yield triketides, tetraketide, etc.[2][3]

 
Biosynthesis of orsellinic acid from polyketide intermediate.

The polyketide chains produced by a minimal polyketide synthase are almost invariably modified. Modifications include reduction of the keto groups to methylene and cyclization. Many of these conversions proceed by the enol tautomers of the polyketide.[4] Polyketides are structurally diverse family.[5] They are broadly divided into three classes: type I polyketides (often macrolides produced by multimodular megasynthases), type II polyketides (often aromatic molecules produced by the iterative action of dissociated enzymes), and type III polyketides (often small aromatic molecules produced by fungal species).

Polyketides are synthesized by multienzyme polypeptides that resemble eukaryotic fatty acid synthase but are often much larger. They include acyl-carrier domains plus an assortment of enzymatic units that can function in an iterative fashion, repeating the same elongation/modification steps (as in fatty acid synthesis), or in a sequential fashion so as to generate more heterogeneous types of polyketides.[2]

ApplicationsEdit

Polyketide antibiotics, antifungals, cytostatics, anticholesteremic, antiparasitics, coccidiostats, animal growth promoters and natural insecticides are in commercial use.[citation needed]

ExamplesEdit

See alsoEdit

ReferencesEdit

  1. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "Polyketides". doi:10.1351/goldbook.P04734
  2. ^ a b Voet, Donald; Voet, Judith G.; Pratt, Charlotte W. (2013). Fundamentals of Biochemistry: Life at the Molecular Level (4th ed.). John Wiley & Sons. p. 688. ISBN 9780470547847.
  3. ^ Staunton, James; Weissman, Kira J. (2001). "Polyketide Biosynthesis: A Millennium Review". Natural Product Reports. 18 (4): 380–416. doi:10.1039/a909079g.
  4. ^ Robinson, John A.; Fersht, Alan Roy; Gani, D. (1991). "Polyketide synthase complexes: Their structure and function in antibiotic biosynthesis". Philos. Trans. R. Soc. Lond. B Biol. Sci. 332 (1263): 107–114. doi:10.1098/rstb.1991.0038. PMID 1678529.
  5. ^ Katz, Leonard (1997). "Manipulation of Modular Polyketide Synthases". Chem. Rev. 97 (7): 2557–2576. doi:10.1021/cr960025+.
  6. ^ Brockmann, Hans; Henkel, Willfried (1951). "Pikromycin, ein bitter schmeckendes Antibioticum aus Actinomyceten" [Pikromycin, a bitter tasting antibiotic from an actinomycete]. Chem. Ber. (in German). 84 (3): 284–288. doi:10.1002/cber.19510840306.