Complex Roles of Insect Cytochrome P450s in Chemical Adaptation

The remarkable success of insects is largely due to their capacity to adapt to various environmental stresses. Central to their ability to cope with chemical challenges, cytochrome P450 monooxygenases (P450s) form a highly diversified superfamily that enables this capacity through extensive functional and evolutionary plasticity. Here, we examine the diversity of insect P450s, including their evolution, classification, and structural features. We bring together recent advances to highlight the intricate and interconnected roles of P450s, which are repeatedly co-opted across diverse mechanisms of chemical adaptation and extend across conventional clan boundaries. By integrating functional, evolutionary, and structural perspectives, we propose a holistic framework in which insect P450s act as cross-mechanism and cross-clan nodes linking detoxification, cuticular penetration, olfaction, and symbiont-mediated chemical adaptation. This framework provides a systems-level perspective on how P450 diversification shapes insect responses to chemically complex environments.