The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling
Autor: | Alexia Chandor-Proust, Jessica Roux, Muhammad Asam Riaz, Jean-Philippe David, Jaclyn Bibby, Mark J. I. Paine, Myriam Régent-Kloeckner, Chantal Dauphin-Villemant, Rodolphe Poupardin, Stéphane Reynaud, Emilie Guittard-Crilat |
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Rok vydání: | 2013 |
Předmět: |
cytochrome P450 monooxygenase
0106 biological sciences Insecticides Anopheles gambiae recombinant system Benzoates 01 natural sciences Biochemistry Insecticide Resistance chemistry.chemical_compound Cytochrome P-450 Enzyme System Aedes 7-OH 7-hydroxycoumarin Pyrethrins 0303 health sciences Pyrethroid pyrethroid Cyt b5 cytochrome b5 Rt retention time qPCR quantitative real-time PCR Cytochrome P450 reductase PBA 3-phenoxybenzoic acid 3. Good health Genetically modified organism Isoenzymes Molecular Docking Simulation qw_52 qx_510 Benzaldehydes qu_26.5 Inactivation Metabolic Insect Proteins Genetic Engineering Oxidation-Reduction Research Article In silico mosquito Saccharomyces cerevisiae Aedes aegypti Biology SRS substrate recognition site Microbiology resistance TFA trifluoroacetic acid 03 medical and health sciences PBAld 3-phenoxybenzaldehyde qx_600 Anopheles parasitic diseases Botany Escherichia coli Animals CPR NADPH-cytochrome P450-reductase Aedes/drug effects Aedes/enzymology Anopheles gambiae/drug effects Anopheles gambiae/enzymology Benzaldehydes/chemistry Benzaldehydes/metabolism Benzoates/metabolism Cytochrome P-450 Enzyme System/chemistry Cytochrome P-450 Enzyme System/genetics Escherichia coli/enzymology Escherichia coli/genetics Insect Proteins/chemistry Insect Proteins/genetics Insect Vectors/drug effects Insect Vectors/enzymology Insecticide Resistance/drug effects Insecticide Resistance/genetics Insecticides/chemistry Insecticides/metabolism Isoenzymes/chemistry Isoenzymes/genetics Metabolic Detoxication Drug NADPH-Ferrihemoprotein Reductase/chemistry NADPH-Ferrihemoprotein Reductase/genetics Pyrethrins/chemistry Pyrethrins/metabolism Saccharomyces cerevisiae/drug effects Saccharomyces cerevisiae/enzymology Molecular Biology NADPH-Ferrihemoprotein Reductase 030304 developmental biology AeCPR Aedes aegypti CPR PBAlc 3-phenoxybenzoic alcohol insecticide wa_240 Cytochrome P450 Cell Biology Monooxygenase biology.organism_classification Insect Vectors 010602 entomology chemistry biology.protein metabolism |
Zdroj: | Biochemical Journal Biochemical Journal, vol. 455, no. 1, pp. 75-85 Biochemical Journal; Vol 455 |
ISSN: | 1470-8728 0264-6021 |
DOI: | 10.1042/bj20130577 |
Popis: | The resistance of mosquitoes to chemical insecticides is threatening vector control programmes worldwide. Cytochrome P450 monooxygenases (CYPs) are known to play a major role in insecticide resistance, allowing resistant insects to metabolize insecticides at a higher rate. Among them, members of the mosquito CYP6Z subfamily, like Aedes aegypti CYP6Z8 and its Anopheles gambiae orthologue CYP6Z2, have been frequently associated with pyrethroid resistance. However, their role in the pyrethroid degradation pathway remains unclear. In the present study, we created a genetically modified yeast strain overexpressing Ae. aegypti cytochrome P450 reductase and CYP6Z8, thereby producing the first mosquito P450–CPR (NADPH-cytochrome P450-reductase) complex in a yeast recombinant system. The results of the present study show that: (i) CYP6Z8 metabolizes PBAlc (3-phenoxybenzoic alcohol) and PBAld (3-phenoxybenzaldehyde), common pyrethroid metabolites produced by carboxylesterases, producing PBA (3-phenoxybenzoic acid); (ii) CYP6Z8 transcription is induced by PBAlc, PBAld and PBA; (iii) An. gambiae CYP6Z2 metabolizes PBAlc and PBAld in the same way; (iv) PBA is the major metabolite produced in vivo and is excreted without further modification; and (v) in silico modelling of substrate–enzyme interactions supports a similar role of other mosquito CYP6Zs in pyrethroid degradation. By playing a pivotal role in the degradation of pyrethroid insecticides, mosquito CYP6Zs thus represent good targets for mosquito-resistance management strategies. The key role of mosquito cytochrome P450 monooxygenases from the CYP6Z subfamily in the resistance of mosquitoes to insecticides was revealed. By using functional expression and in silico modelling, the capacity of CYP6Zs to degrade insecticide metabolites produced by esterase-mediated hydrolysis was demonstrated. |
Databáze: | OpenAIRE |
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