Polyketide

Polyketides are secondary metabolites from bacteria, fungi, plants, and animals. Polyketides are usually biosynthesized through the decarboxylative condensation of malonyl-CoA derived extender units in a similar process to fatty acid synthesis (a Claisen condensation). The polyketide chains produced by a minimal polyketide synthase are often further derivitized and modified into bioactive natural products.

Polyketides are structurally a very diverse family of natural products with diverse biological activities and pharmacological properties. They are broadly divided into three classes: type I polyketides (often macrolides produced by mutimodular 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). Polyketide antibiotics, antifungals, cytostatics, anticholesteremic, antiparasitics, coccidiostats, animal growth promoters and natural insecticides are in commercial use.

Examples

• Macrolides
  • Pikromycin, the first isolated macrolide (1950)
  • The antibiotics erythromycin A, clarithromycin, and azithromycin
  • The immunosuppressant tacrolimus (FK506)
  • Radicicol and Pochonin family (HSP90 inhibitor)
• Polyene antibiotics
  • Amphotericin
• Tetracyclines
  • The tetracycline family of antibiotics
• Acetogenins
  • Annonacin
  • Uvaricin
• Others
  • Discodermolide
  • Aflatoxin
  • Usnic acid

Biosynthesis

Polyketides are synthesized by one or more specialized and highly complex polyketide synthase (PKS) enzymes.

See also

• Esterase
• Nonribosomal peptide