The cyclic keto-enol insecticide spirotetramat inhibits insect and spider mite acetyl-CoA carboxylases by interfering with the carboxyltransferase partial reaction

Abstract

Acetyl-CoA carboxylase (ACC) catalyzes the committed and rate-limiting step in fatty acid biosynthesis. The two partial reactions, carboxylation of biotin followed by carboxyl transfer to the acceptor acetyl-CoA, are performed by two separate domains in animal ACCs. The cyclic keto-enol insecticides and acaricides have been proposed to inhibit insect ACCs. In this communication, we show that the enol derivative of the cylic keto-enol insecticide spirotetramat inhibited ACCs partially purified from the insect species Myzus persicae and Spodoptera frugiperda, as well as the spider mite (Tetranychus urticae) ACC which was expressed in insect cells using a recombinant baculovirus. Steady-state kinetic analysis revealed competitive inhibition with respect to the carboxyl acceptor, acetyl-CoA, indicating that spirotetramat-enol bound to the carboxyltransferase domain of ACC. Interestingly, inhibition with respect to the biotin carboxylase substrate ATP was uncompetitive, which may indicate that the keto-enol binding site was formed following long-range conformational change triggered by ATP binding. Amino acid residues in the carboxyltransferase domains of plant ACCs are important for binding of established herbicidal inhibitors. Mutating the spider mite ACC at the homologous positions, for example L1736 to either isoleucine or alanine, and A1739 to either valine or serine, did not affect the inhibition of the spider mite ACC by spirotetramat-enol. These results indicated different binding modes of the keto-enols and the herbicidal chemical families.

The economic importance of acaricides in the control of phytophagous mites and an update on recent acaricide mode of action research

“…Steadystate kinetics of ACC inhibition by spirotetramat enol revealed that the inhibition was competitive with regard to the substrate acetylCoA, indicating that the compound binds to the carboxyltransferase domain of ACC. A mutation analysis of the spider mite enzyme, focusing on conserved residues implicated in resistance to herbicidal ACC inhibitors, did not reveal altered inhibitor binding, suggesting a different binding mode between acaricidal keto-enols and the herbicidal compounds [65].…”

“…This not only fitted the observed poisoning symptoms but also the fact that these compounds were developed out of acylated derivatives of an herbicidal precursor with known action on ACC. However, biochemical investigations on the interactions between keto-enol acaricides and ACC have only recently been presented [65]. In the study of Lümmen et al [65], ACC enzyme preparations were purified from Myzus persicae and Spodoptera frugiperda and the T. urticae ACC was recombinantly expressed and purified with a baculovirus system in insect cells.…”

“…However, biochemical investigations on the interactions between keto-enol acaricides and ACC have only recently been presented [65]. In the study of Lümmen et al [65], ACC enzyme preparations were purified from Myzus persicae and Spodoptera frugiperda and the T. urticae ACC was recombinantly expressed and purified with a baculovirus system in insect cells. Using these preparations, it was shown that the enol derivative of spirotetramat (Fig.…”

Hypoglycemia and revisable ST-elevation induced by Movento

“…MCA is the rate limiting steps of fatty acid biosynthesis. [5] There are two isoforms of ACC in human, Type 1 and 2. Type 1 is a cytosolic ACC in lipogenic tissues and ACC2 is a mitochondrial enzyme in heart and liver tissues.…”

Over-expression of CYP6A2 is associated with spirotetramat resistance and cross-resistance in the resistant strain of Aphis gossypii Glover

“…Spirotetramat is instantly transformed to spirotetramat-enol in the plant after leaf uptake, which is distributed throughout the plant due to the insecticide's favorable physicochemical properties. Spirotetramat-enol inhibits Myzus persicae, Spodoptera frugiperda, as well as Tetranychus urticae ACC by interfering with the carboxyl transferase partial reaction [12]. Research indicated that one amino acid substitution (E645K) in the biotin carboxylase domain of the ACC gene is associated with spiromesifen resistance in Trialeurodes vaporariorum [13].…”