The shikimate pathway and its branches in apicomplexan parasites

J Infect Dis. 2002 Feb 15:185 Suppl 1:S25-36. doi: 10.1086/338004.

Abstract

The shikimate pathway is essential for production of a plethora of aromatic compounds in plants, bacteria, and fungi. Seven enzymes of the shikimate pathway catalyze sequential conversion of erythrose 4-phosphate and phosphoenol pyruvate to chorismate. Chorismate is then used as a substrate for other pathways that culminate in production of folates, ubiquinone, napthoquinones, and the aromatic amino acids tryptophan, phenylalanine, and tyrosine. The shikimate pathway is absent from animals and present in the apicomplexan parasites Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum. Inhibition of the pathway by glyphosate is effective in controlling growth of these parasites. These findings emphasize the potential benefits of developing additional effective inhibitors of the shikimate pathway. Such inhibitors may function as broad-spectrum antimicrobial agents that are effective against bacterial and fungal pathogens and apicomplexan parasites.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apicomplexa / growth & development
  • Apicomplexa / metabolism*
  • Gene Expression Regulation
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Glyphosate
  • Molecular Sequence Data
  • Phosphorus-Oxygen Lyases / chemistry
  • Phosphorus-Oxygen Lyases / genetics
  • Phosphorus-Oxygen Lyases / metabolism
  • Shikimic Acid / antagonists & inhibitors
  • Shikimic Acid / metabolism*

Substances

  • Shikimic Acid
  • chorismate synthase
  • Phosphorus-Oxygen Lyases
  • Glycine