The carboxyltransferase activity of the apicoplast acetyl-CoA carboxylase of Toxoplasma gondii is the target of aryloxyphenoxypropionate inhibitors.
Inhibition of growth of the apicomplexan parasite Toxoplasma gondii by aryloxyphenoxypropionate herbicides has been correlated with the inhibition of its acetyl-CoA carboxylase (ACC) by these compounds. Here, full-length and C-terminal fragments of T. gondii apicoplast ACC as well as C-terminal fragments of the cytosolic ACC were expressed in Escherichia coli. The recombinant proteins that were soluble showed the expected enzymatic activities. Yeast gene-replacement strains depending for growth on the expressed T. gondii ACC were derived by complementation of a yeast ACC1 null mutation. In vitro and in vivo tests with aryloxyphenoxypropionates showed that the carboxyltransferase domain of the apicoplast T. gondii ACC is the target for this class of inhibitors. The cytosolic T. gondii ACC is resistant to aryloxyphenoxypropionates. Both T. gondii isozymes are resistant to cyclohexanediones, another class of inhibitors targeting the ACC of grass plastids.
Jelenska
Joanna
J
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA.
Sirikhachornkit
Anchalee
A
Haselkorn
Robert
R
Gornicki
Piotr
P
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D019878:Carboxyl and Carbamoyl Transferases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D005227:Fatty Acids / Q000096:biosynthesis; D006540:Herbicides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014122:Toxoplasma / Q000187:drug effects / Q000201:enzymology*
D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D006540:Herbicides; D011994:Recombinant Proteins; D019878:Carboxyl and Carbamoyl Transferases; D000103:Acetyl-CoA Carboxylase