Molecular Basis for the Selectivity of the Succinate Dehydrogenase Inhibitor Cyflumetofen between Pest and Predatory Mites.
Molecular Basis for the Selectivity of the Succinate Dehydrogenase Inhibitor Cyflumetofen between Pest and Predatory Mites.
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DOI：
10.1021/acs.jafc.2c06149
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发表时间：
2023-02
影响因子：
6.1
通讯作者：
Jinhang Li;P. Wei;Juan Qin;K. Feng;G. Shen;W. Dou;Y. Zhang;Pengyu Cao;Z. Yuchi;T. Van Leeuwen;Lin He
中科院分区：
文献类型：
--
作者：
Jinhang Li;P. Wei;Juan Qin;K. Feng;G. Shen;W. Dou;Y. Zhang;Pengyu Cao;Z. Yuchi;T. Van Leeuwen;Lin He
作为线粒体琥珀酸脱氢酶（SDHI）抑制剂的杀螨剂提供了对植食性螨的优异控制，但对捕食性螨和其他有益生物显示出有限的毒性。然而，选择性的分子机制尚未完全理解。在这里，我们首先确认SDHI杀螨剂对蜘蛛螨的毒性比捕食螨高10，000倍以上。接下来，我们表明，差异渗透，促杀螨剂激活，或代谢最有可能不是这种选择性的主要原因。相比之下，AB-1对SDH靶标的抑制作用在叶螨中比在捕食螨中强约200倍，揭示了强的靶位点选择性。引人注目的是，在果蝇中通过基因编辑鉴定并验证了与差异结合相关的关键基序。我们的研究结果有助于了解SDHI的选择性，这可以用于选择性杀螨剂的合理设计，以支持综合害虫管理。
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.