The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling

In this study, we created a genetically modified yeast strain over-expressing Ae. aegypti cytochrome P450 reductase and CYP6Z8, thereby producing the first mosquito P450/CPR complex in a yeast recombinant system. Our results showed that: (1) CYP6Z8 metabolizes 3-phenoxybenzoic alcohol (PBAlc) and 3-phenoxybenzaldehyde (PBAld), common pyrethroid metabolites produced by carboxylesterases, producing 3-phenoxybenzoic acid (PBA); (2) CYP6Z8 transcription is induced by PBAlc, PBAld and PBA; (3) A. gambiae CYP6Z2 metabolizes PBAlc and PBAld in the same way; (4) PBA is the major metabolite produced in vivo and is excreted without further modification; and (5) in silico modeling 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.
Source: BJ Gene - Category: Biochemistry Authors: Tags: BJ Metabolism Source Type: research