Quercetin glycosylation and hydrolysis mediate a biochemical arms race between apple and herbivorous insects

Quercetin glycosides are abundant flavonoids in apple (Malus domestica) leaves; however, how their structural variation shapes plant-insect interactions remain unclear. Here, we show that quercetin glycosylation and hydrolysis underlie a biochemical arms race between apple and multiple herbivorous insects. Herbivory by Helicoverpa armigera and Spodoptera litura activated a jasmonic acid (JA)-regulated transcriptional response that selectively induced the quercetin-glycoside pathway, resulting in elevated accumulation of 5 major quercetin glycosides. Methyl jasmonate treatment and JA content-boosting transgenic plants increased quercetin glycosides, whereas altering quercetin glycoside content did not feedback to JA signaling. Functional analyses revealed strong structure-dependent variation in anti-insect activity. Quercetin 3-O-glucoside (Q3Glc), but not its isomer quercetin 3-O-galactoside (Q3Gal), deterred larval feeding. During herbivory, apple leaves hydrolyzed Q3Glc to release toxic quercetin, while insects displayed species-specific detoxification strategies. H. armigera and S. exigua re-glycosylated quercetin to regenerate Q3Glc, neutralizing toxicity, whereas S. litura and S. frugiperda lacked this ability and suffered reduced growth. These findings reveal a reciprocal metabolic interplay in which apple activates glycoside hydrolysis to deploy toxic aglycones, while insects counter-evolve re-glycosylation to attenuate toxicity. Quercetin glycosylation patterns, therefore, serve as dynamic determinants of apple defense and herbivore susceptibility, offering opportunities for breeding insect-resistant cultivars.