Abstract

Introduction Uridine diphosphate (UDP) glycosyltransferases (UGTs) are a major class of detoxifying enzymes that metabolize xenobiotics through glycosylation. Although UGTs are widely implicated in insect resistance to plant secondary metabolites (PSMs), their functions in adapting to host plant flavonoids remain unclear. Objective Revealing the function of UGT in the adaptation of the silkworm to mulberry flavonoids. Methods In this study, we investigated the function of Bombyx mori UGT40K1 (BmUGT40K1) using a multi-methodological approach that integrated in vitro enzyme activity detected by HPLC-MS/MS, transgenic overexpression, and CRISPR/Cas9-mediated knockout. Results The results showed that flavonoid treatment on silkworm induces physiological and developmental impairments similar to those caused by UGT inhibitors. In vitro   enzyme assays confirmed that BmUGT40K1, which is predominantly expressed in detoxification organs such as midgut during the larval feeding stage, is a crucial enzyme capable of metabolizing these flavonoids. Functional studies further revealed that BmUGT40K1 not only directly facilitates flavonoid detoxification but also modulates the activities of other detoxification enzymes and oxidoreductases. Conclusion BmUGT40K1   plays a central role in flavonoid resistance and likely serves as an important mediator of antioxidant capacity in silkworm. These findings deepen our fundamental understanding of insect-plant coevolution and adaptive responses to phytochemicals.