Cytochrome P450 monooxygenases (P450s; encoded by the <i>CYP</i> genes) are a remarkable superfamily of enzymes found in all kingdoms of life that can catalyze a diverse array of oxidative transformations of both endogenous and exogenous substrates, including natural and synthetic xenobiotics. The recent explosion in research on the complete complement of P450 genes, the “CYPome”, in arthropods is, in part, a reflection of the dramatic increase in the number of invertebrate genomes sequenced. Recent advances in insect genomics and post-genomic functional approaches have provided an unprecedented opportunity to understand their role in insect toxicology. This includes the detoxification of insecticides in crop pests and disease vectors leading to resistance, and in bee pollinators, where P450s have been recently shown to act as key determinants of insecticide selectivity. The knowledge gained from these studies has applications for the management of P450-mediated resistance in insect pests and can be leveraged to safeguard the health of important beneficial insects. One of the most exciting findings in the last decade, the documentation of P450-based pesticide selectivity in bee pollinators at the molecular level, has opened novel molecular options for mechanistic pesticide risk assessment in bee pollinators using recombinant P450 libraries. Screening of functionally expressed bee pollinator P450s may become a standard procedure in future insecticide development, just as screening of the major human liver P450s is now standard in the development of new drugs.

Toxicogenomic approaches addressing cytochrome P450 mediated insecticide selectivity

ACS Fall 2021

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