Cytochrome P450 Gene Cyp6A14 Mediates Quercetin Detoxification in Thitarodes xiaojinensis Larvae

Thitarodes xiaojinensis larvae, obligate hosts of Ophiocordyceps sinensis, feed on Polygonum viviparum roots rich in quercetin, a defensive flavonoid that is toxic to many herbivorous insects. However, the molecular mechanism underlying their quercetin tolerance remains unclear. Here, we show that T. xiaojinensis larvae tolerate high quercetin exposure and identify the cytochrome P450 gene Cyp6A14 as a key detoxification factor. Quercetin treatment strongly induced the Cyp6A14 expression. RNA interference reduced Cyp6A14 transcript levels by 85.1% and significantly increased larval mortality under quercetin stress. High-performance liquid chromatography further showed that Cyp6A14 silencing caused marked accumulation of quercetin in larval hemolymph, indicating impaired Phase I detoxification. Phylogenetic analyses suggest functional adaptation of Cyp6A14 toward efficient quercetin metabolism. These findings reveal a molecular basis for quercetin tolerance and provide guidance for developing chemically compatible artificial diets for T. xiaojinensis rearing.