The shikimate pathway and its branches in apicomplexan parasites.
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.
Roberts
Craig W
CW
Department of Immunology, University of Strathclyde, Glasgow, United Kingdom.
Roberts
Fiona
F
Lyons
Russell E
RE
Kirisits
Michael J
MJ
Mui
Ernest J
EJ
Finnerty
John
J
Johnson
Jennifer J
JJ
Ferguson
David J P
DJ
Coggins
John R
JR
Krell
Tino
T
Coombs
Graham H
GH
Milhous
Wilbur K
WK
Kyle
Dennis E
DE
Tzipori
Saul
S
Barnwell
John
J
Dame
John B
JB
Carlton
Jane
J
McLeod
Rima
R
D000595:Amino Acid Sequence; D000818:Animals; D016782:Apicomplexa / Q000254:growth & development / Q000378:metabolism*; D005786:Gene Expression Regulation; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012765:Shikimic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097797:Glyphosate
D005998:Glycine; D019761:Phosphorus-Oxygen Lyases; D012765:Shikimic Acid; D000097797:Glyphosate; C019895:chorismate synthase