title: Apicoplast acetyl Co-A carboxylase of the human malaria parasite is not targeted by cyclohexanedione herbicides.
abstract: Malaria parasites retain a relict plastid (apicoplast) from a photosynthetic ancestor. The apicoplast is a useful drug target but the specificity of compounds believed to target apicoplast fatty acid biosynthesis has become uncertain, as this pathway is not essential in blood stages of the parasite. Herbicides that inhibit the plastid acetyl Coenzyme A (Co-A) carboxylase of plants also kill Plasmodium falciparum in vitro, but their mode of action remains undefined. We characterised the gene for acetyl Co-A carboxylase in P. falciparum. The P. falciparum acetyl-CoA carboxylase gene product is expressed in blood stage parasites and accumulates in the apicoplast. Ablation of the gene did not render parasites insensitive to herbicides, suggesting that these compounds are acting off-target in blood stages of P. falciparum.
authors.affiliation: School of Botany, University of Melbourne, Victoria 3010, Australia.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Goodman
authors.affiliation: School of Botany, University of Melbourne, Victoria 3010, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mollard
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Theola
authors.initials: T
authors.lastname: Louie
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Georgina A
authors.initials: GA
authors.lastname: Holloway
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Watson
authors.affiliation: School of Botany, University of Melbourne, Victoria 3010, Australia. Electronic address: gim@unimelb.edu.au.
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: McFadden
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism*; D063546:Apicoplasts / Q000201:enzymology*; D003512:Cyclohexanones / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006540:Herbicides / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology*
chemical_list: D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D006540:Herbicides; D000103:Acetyl-CoA Carboxylase
keywords: Acetyl Co-A carboxylase; Apicoplast; Fatty acid biosynthesis; Herbicides; Malaria