Oxytetracycline biosynthesis

J Biol Chem. 2010 Sep 3;285(36):27509-15. doi: 10.1074/jbc.R110.130419. Epub 2010 Jun 3.


Oxytetracycline (OTC) is a broad-spectrum antibiotic that acts by inhibiting protein synthesis in bacteria. It is an important member of the bacterial aromatic polyketide family, which is a structurally diverse class of natural products. OTC is synthesized by a type II polyketide synthase that generates the poly-beta-ketone backbone through successive decarboxylative condensation of malonyl-CoA extender units, followed by modifications by cyclases, oxygenases, transferases, and additional tailoring enzymes. Genetic and biochemical studies have illuminated most of the steps involved in the biosynthesis of OTC, which is detailed here as a representative case study in type II polyketide biosynthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry
  • Cyclization
  • Drug Resistance, Bacterial / genetics
  • Macrolides / metabolism
  • Oxytetracycline / biosynthesis*
  • Oxytetracycline / chemistry
  • Tetracyclines / metabolism


  • Anti-Bacterial Agents
  • Macrolides
  • Tetracyclines
  • 4-epianhydrotetracycline
  • Oxytetracycline