CYP4CE1 Metabolized\nNitenpyram through Two Types of\nOxidation Reaction, Hydroxylation, and N‑Demethylation

Nitenpyram, taking the place of imidacloprid, is a widely\nused\nneonicotinoid insecticide to control Nilaparvata lugens in Asia. Two P450s, CYP4CE1 and CYP6ER1, are key factors in the\nmetabolic resistance against nitenpyram and imidacloprid. In this\nstudy, we found that <i>CYP4CE1</i> expression was strongly\nassociated with nitenpyram resistance in 8 field-collected populations,\nwhereas <i>CYP6ER1</i> expression correlated with imidacloprid\nresistance. Hence, we focused on nitenpyram metabolism by CYP4CE1,\ndue to that imidacloprid metabolism by CYP6ER1 has intensively investigated.\nMass spectrometry analysis revealed that recombinant CYP4CE1 metabolized\nnitenpyram into three products, N-desmethyl nitenpyram, hydroxy-nitenpyram,\nand N-desmethyl hydroxy-nitenpyram, with a preference for hydroxylation.\nIn contrast, CYP6ER1 metabolized nitenpyram into a single product,\nN-desmethyl nitenpyram. These results provide new insights into the\nspecific catalytic mechanisms of P450 enzymes in neonicotinoid metabolism\nand underscore the importance of different catalytic reactions in\nneonicotinoid insecticide resistance.