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The shikimate pathway and its branches in apicomplexan parasites

Roberts, C W and Roberts, F and Lyons, R E and Kirisits, M J and Mui, E J and Finnerty, J and Johnson, J J and Ferguson, D J P and Coggins, J R and Krell, T and Coombs, G H and Milhous, W K and Kyle, D E and Tzipori, S and Barnwell, J and Dame, J B and Carlton, J and McLeod, R and Roberts, Craig (2002) The shikimate pathway and its branches in apicomplexan parasites. Journal of Infectious Diseases, 185 (Supple). S25-S36. ISSN 0022-1899

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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.