The common cutworm, Spodoptera litura, has developed with varying degrees of resistance to most commonly used insecticides. Cytochrome P450 monooxygenases (P450s) with broad substrate specificities have been frequently reported to be involved in insecticide detoxification, but the underlying mechanisms remain obscure. Herein, seven CYP6AE subfamily P450s which possess six classical substrate recognition sites and several conserved catalytic motifs were identified from the genome of S. litura. Spatiotemporal expression profiles showed that these CYP6AE subfamily members were predominantly expressed in the larval midgut. Among them, CYP6AE43 and CYP6AE48 were significantly induced by three pyrethroids including β-cypermethrin, λ-cyhalothrin and fenvalerate. Knockdown of CYP6AE43 or CYP6AE48 by RNA interference dramatically increased the larval susceptibility to the pyrethroids. When silencing them simultaneously, the larval susceptibility to pyrethroids was higher than when silencing them individually, indicating a cooperative relationship between these two P450s in pyrethroid detoxification. Homology modeling and molecular docking analyses showed that these three pyrethroids could stably bind to CYP6AE43 and CYP6AE48, with the binding free energies from −37.58 to −84.24 kcal mol⁻¹. These results indicate that induction of CYP6AE43 and CYP6AE48 contributes to pyrethroid detoxification and promotes the development of resistance to pyrethroids in S. litura.

常见的地老虎（Spodoptera litura）对最常用的杀虫剂具有不同程度的抗性。据报道，具有广泛底物特异性的细胞色素 P450 单加氧酶 (P450s) 经常参与杀虫剂解毒，但其潜在机制仍不清楚。在此，从斜纹草的基因组中鉴定出具有六个经典底物识别位点和几个保守催化基序的七个 CYP6AE 亚科P450。时空表达谱显示这些CYP6AE亚家族成员主要在幼虫中肠中表达。其中，CYP6AE43和CYP6AE48β-氯氰菊酯、λ-三氯氟氰菊酯和氰戊菊酯三种拟除虫菊酯显着诱导。通过 RNA 干扰敲除 CYP6AE43或CYP6AE48显着增加了幼虫对拟除虫菊酯的敏感性。当同时沉默它们时，幼虫对拟除虫菊酯的敏感性高于单独沉默它们时，表明这两种 P450 在拟除虫菊酯解毒中存在协同关系。同源性建模和分子对接分析表明，这三种拟除虫菊酯可以稳定地与CYP6AE43和CYP6AE48结合，结合自由能从-37.58到-84.24 kcal mol ^-1。这些结果表明CYP6AE43的诱导和CYP6AE48有助于拟除虫菊酯解毒并促进斜纹菊对拟除虫菊酯的抗性发展。