sethoxydim and fluazifop

Trypanosoma brucei, a eukaryotic pathogen that causes African sleeping sickness in humans and nagana in cattle, depends on the enzyme acetyl-CoA carboxylase (ACC) for full virulence in mice. ACC produces malonyl-CoA, the two carbon donor for fatty acid synthesis. We assessed the effect of haloxyfop, an aryloxyphenoxypropionate herbicide inhibitor of plastid ACCs in many plants as well as Toxoplasma gondii, on T. brucei ACC activity and growth in culture. Haloxyfop inhibited TbACC in cell lysate (EC(50) 67 μM), despite the presence of an amino acid motif typically associated with resistance. Haloxyfop also reduced growth of bloodstream and procyclic form parasites (EC(50) of 0.8 and 1.2 mM). However, the effect on growth was likely due to off-target effects because haloxyfop treatment had no effect on fatty acid elongation or incorporation into complex lipids in vivo.

Topics: Acetyl-CoA Carboxylase; Amino Acid Sequence; Cyclohexanones; Dihydropyridines; Enzyme Inhibitors; Fatty Acids; Propionates; Pyridines; Quinoxalines; Sequence Alignment; Trypanosoma brucei brucei

Resistance to aryloxyphenoxypropionate (AOPP), cyclohexanedione (CHD) and phenylurea herbicides was determined in UK populations of Alopecurus myosuroides Huds. Two populations (Oxford AA1, Notts. A1) were highly resistant (Resistance indices 13-->1000) to the AOPP and CHD herbicides fenoxaprop, diclofop, fluazifop-P and sethoxydim, but only marginally resistant to the phenylurea, chlorotoluron. Analyses of acetyl coenzyme A carboxylase (ACCase) activity showed that an insensitive ACCase conferred resistance to all the AOPP/CHD herbicides investigated. Another population, Oxford S1, showed no resistance to sethoxydim at the population level, but contained a small proportion of plants (<10%) with an insensitive ACCase. Genetic studies on the Notts A1 and Oxford S1 populations demonstrated that target site resistance conferred by an insensitive ACCase is monogenic, nuclearly inherited with the resistant allele showing complete dominance. Investigations of the molecular basis of resistance in the Notts A1 population showed that sethoxydim resistance in A myosuroides was associated with the substitution of an isoleucine in susceptible with a leucine in resistant plants, which has also been found in three other resistant grass-weed species (Setaria viridis (L) Beauv, Avena fatua L, Lolium rigidum Gaud).

Topics: Acetyl-CoA Carboxylase; Binding Sites; Cyclohexanones; Dihydropyridines; Dose-Response Relationship, Drug; Drug Resistance; Environment, Controlled; Genetic Complementation Test; Halogenated Diphenyl Ethers; Herbicides; Oxazoles; Phenyl Ethers; Phenylurea Compounds; Poaceae; Propionates

The importance of acetyl-CoA carboxylase in regulation of lipid synthesis for barley and maize leaves has been quantitatively assessed using, as specific inhibitors, the herbicides fluazifop and sethoxydim. Apparent flux control coefficients of about 0.58 and 0.52 were determined for acetyl-CoA carboxylase in barley and maize leaves, respectively. These results show that acetyl-CoA carboxylase is the major flux controlling enzyme for light-stimulated lipid synthesis in these tissues.

Topics: Acetyl-CoA Carboxylase; Cyclohexanones; Dihydropyridines; Herbicides; Hordeum; Lipids; Zea mays

Topics: Chloroplasts; Cyclohexanones; Dihydropyridines; Herbicides; Lipid Metabolism; Poaceae; Propionates; Quinoxalines; Zea mays