Molecular Basis for the Selectivity of the Succinate Dehydrogenase Inhibitor Cyflumetofen between Pest and Predatory Mites

Abstract

Acaricides that act as inhibitors of the mitochondrial succinate dehydrogenase (SDHIs) provide excellent control of phytophagous mites but display limited toxicity to predatory mites and other beneficial organisms. However, the molecular mechanism of selectivity is not fully understood. Here, we first confirm that SDHI acaricides are over 10,000-fold more toxic to spider mites than predatory mites. Next, we show that differential penetration, pro-acaricide activation, or metabolism are most likely not the main reason for this selectivity. In contrast, the inhibition of AB-1 on the SDH target is approximately 200-fold more potent in spider mites compared to predatory mites, revealing strong target-site selectivity. Strikingly, a key motif associated with differential binding was identified and validated by gene editing in Drosophila. Our findings contribute to understanding the selectivity of SDHIs, which can be used for the rational design of selective acaricides in support of an integrated pest management.

Development of Sustainable Insecticide Candidates for Protecting Pollinators: Insight into the Bioactivities, Selective Mechanism of Action and QSAR of Natural Coumarin Derivatives against Aphids

“…Reverse genetics strategy using gene-editing flies has emerged as a powerful tool for identifying action targets of insecticides. 21,23,63 Recently, a study, using engineered Drosophila, has identified nicotinamidase, which is expressed in mechanoreceptor neurons, as a novel molecular target for an insecticide flonicamid. 63 We used gene-editing Drosophila, in this study, to demonstrate that Lys585 in aphid AgAChE was the speciesspecific binding site of 6-methylcoumarin.…”

“…Many frequently used insecticides, such as organophosphates (OPs), carbamates (CMs), and neonicotinoids, are toxic to pollinators because their action sites are commonly highly conserved in insects. Fortunately, the differences in target sites, such as octopamine receptor, 21 sodium channel, 22 and mitochondrial succinate dehydrogenase, 23 may confer selective toxicity of some insecticides on beneficial organisms and pests. quently, the strain of aphids was reared on robust Gossypium hirsutum seedlings using a caging method in a greenhouse at 26 ± 1 °C, 70% relative humidity, and a 14 h:10 h (light:dark) photoperiod.…”

3D-QSAR-Directed Synthesis of Halogenated Coumarin-3-Hydrazide Derivatives: Unveiling Their Potential as SDHI Antifungal Agents

“…Succinate dehydrogenase inhibitors (SDHIs), a class of widely deployed fungicides, have played a pivotal role in global agricultural disease management since their discovery in the early 1960s. These compounds exert their action by disrupting the cellular respiration of pathogenic fungi through the inhibition of succinate dehydrogenase. − Currently, Figure B illustrates the primary amide SDHIs varieties that have been introduced in recent years. These compounds hold immense importance in the prevention and treatment of pathogenic fungi …”

Discovery of Novel Aminocyclobutanecarboxylic Acid Derivatives as Succinate Dehydrogenase Inhibitors

“…Especially, one of the key enzymes of mitochondrial respiration is succinate dehydrogenase. Succinate dehydrogenase inhibitors (SDHIs), featuring a unique mechanism of action, diverse structures, and high antifungal efficiency, − have been used to suppress hazardous plant pathogenic fungi such as Pyricularia oryzae, Puccinia recondita, Rhizoctonia solani, Sclerotinia sclerotiorum, and Botrytis cinerea. Bearing the common characteristics of molecular structures, these commercial SDHIs mainly consisted of three parts including a polar segment, an amide linker, and a hydrophobic tail.…”