Li Xiaokun, Ma Lixin, Yang Wenjia, Xu Kangkang
Key Laboratory of Surveillance and Management of Invasive Alien Species in Guizhou Education Department, Guiyang University, Guiyang, China.
Front Physiol. 2024 Nov 20;15:1503953. doi: 10.3389/fphys.2024.1503953. eCollection 2024.
Insect cytochrome P450 monooxygenases (CYPs) play crucial roles in the metabolic detoxification of insecticides. Ethyl formate and benzothiazole have recently regained popularity as fumigants due to rising resistance to phosphine in the stored-product pests. However, the mechanisms underlying tolerance to these two fumigants in , a major global insect pest of stored products, remain poorly understood. In this study, two genes, named and , were identified from , belonging to the CYP6 family and containing five conserved domains characteristic of CYP proteins. Spatiotemporal expression analysis revealed that both genes were predominantly expressed in the larval stage and showed the highest expression in the foregut. Upon exposure to ethyl formate and benzothiazole, both genes were upregulated, with significantly increased transcription levels following treatment. RNA interference-mediated silencing of and led to increased susceptibility and significantly higher mortality of when exposed to these fumigants. Homology modeling and molecular docking analyses showed stable binding of these fumigants to CYP6SZ3 and CYP6AEL1 proteins, with binding free energies from -26.88 to -94.68 kcal mol. These findings suggest that the induction of and is likely involved in the detoxification of ethyl formate and benzothiazole in .
昆虫细胞色素P450单加氧酶（CYPs）在杀虫剂的代谢解毒中起着关键作用。由于储粮害虫对磷化氢的抗性不断增强，甲酸乙酯和苯并噻唑作为熏蒸剂最近重新受到关注。然而，对于全球主要储粮害虫米象对这两种熏蒸剂的耐受机制仍知之甚少。在本研究中，从米象中鉴定出两个基因，命名为CYP6SZ3和CYP6AEL1，它们属于CYP6家族，包含CYP蛋白特有的五个保守结构域。时空表达分析表明，这两个基因主要在幼虫阶段表达，在前肠中表达量最高。暴露于甲酸乙酯和苯并噻唑后，这两个基因均上调，处理后转录水平显著增加。RNA干扰介导的CYP6SZ3和CYP6AEL1沉默导致米象在接触这些熏蒸剂时易感性增加且死亡率显著提高。同源建模和分子对接分析表明，这些熏蒸剂与CYP6SZ3和CYP6AEL1蛋白稳定结合，结合自由能为-26.88至-94.68 kcal mol。这些发现表明，CYP6SZ3和CYP6AEL1的诱导可能参与米象对甲酸乙酯和苯并噻唑的解毒过程。
