Single amino acid variations drive functional divergence of cytochrome P450s in Helicoverpa species

Multiple-P450 Gene Co-Up-Regulation in the Development of Permethrin Resistance in the House Fly, Musca domestica

“…Using coupled CRISPR-Cas9-based genome editing techniques and in vitro metabolism analysis, Wang et al [ 47 ] approved a cluster of nine P450 genes involved in the metabolism of xenobiotics in cotton bollworms, Helicoverpa armigera . While many studies have revealed that the overexpression of P450 genes is regulated by unknown trans- or cis-regulatory factors [ 1 , 11 , 26 , 27 , 43 , 44 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ], mutations in P450 proteins have also been proven to impact the xanthotoxin metabolism of P450s [ 55 ]. Taken together, these studies have demonstrated not only that insecticide resistance in a single insect is conferred by the co-contribution of multiple P450 genes, but also that the interaction with regulatory factors plays an important role.…”

CYP321A Subfamily P450s Contribute to the Detoxification of Phytochemicals and Pyrethroids in Spodoptera litura

“…litura, the CYP321A subfamily may also participate in the detoxification of xenobiotics in this insect species. In general, the catalytic activity and metabolic efficiency of P450s are mainly affected by the three-dimensional structure, especially the key residues that determine the size and conformation of the active site . Among them, six SRSs with highly variable amino acid sequences are proposed to form important domains and account for the functional divergence of P450s .…”

“…Herbivorous insects are frequently encountered by an array of xenobiotics, including natural compounds such as defensive phytochemicals derived from their host plants and synthetic insecticides of anthropogenic origin. To cope with these challenges, insects have developed a wide variety of detoxification enzymes that metabolize the toxins, thus conferring their capacity to survive upon exposure to variable environments. , Cytochrome P450 monooxygenases (P450s), a superfamily of heme-thiolate proteins, act as an important class of phase I detoxification enzymes that participate in the metabolism of both endogenous and exogenous compounds. , Due to their structure-derived functional divergence, broad substrate binding specificity, and genetic versatility, cytochrome P450s-mediated detoxification has been confirmed as a major resistance mechanism to various phytochemicals and insecticides in herbivorous insects. , In general, the catalytic enzyme properties and substrate profiles of P450s are mainly determined by their three-dimensional structures, especially the key residues that determine active site formation and shape. , Numerous reports have indicated that six substrate recognition sites (SRS1–6) with highly variable amino acid sequences shape the catalytic sites and substrate access channels, thus defining the P450 enzyme activities and substrate ranges. , …”

CYP4CL2 Confers Metabolic Resistance to Pyridaben in the Citrus Pest Mite Panonychus citri

“…To identify the amino acids within each substrate recognition site (SRS) of CYP4CL2, the primary sequence was aligned with that of HaCYP6AE19 using Clustal Omega . A model of the CYP4CL2 enzyme was generated using AlphaFold2 by submitting the primary sequence to the ColabFold Website and running AlphaFold2 with default options.…”

“…Molecular Modeling and Pyridaben Docking Analysis. The SRSs of CYP4CL2 were identified using the sequence of another P450 (HaCYP6AE19) 29 as reference (Figure S3). A model of CYP4CL2 was then generated to determine whether pyridaben could be accommodated within its active site.…”