Cytochrome P450 6M2 from the malaria vector Anopheles gambiae metabolizes pyrethroids: Sequential metabolism of deltamethrin revealed.

摘要: Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is a major threat control programmes. Cytochome P450-mediated detoxification an important resistance mechanism. CYP6M2 over-expressed wild populations of permethrin resistant A. but its role not clear. was expressed Escherichia coli and structural model produced examine metabolism. Both deltamethrin were metabolized. Rates enhanced by cytochrome b(5) with kinetic parameters K(M)=11±1μM k(cat)=6.1±0.4 per min for (1:1 cis-trans) K(M)=2.0±0.3μM k(cat)=1.2±0.1 deltamethrin. Mass spectrometry NMR analysis identified 4'-hydroxy hydroxymethyl as minor metabolites respectively. Secondary breakdown products included cyano(3-hydroxyphenyl)methyl deltamethrate deltamethric acid. most highly transcribed midgut Malpighian tubules adult gambiae, consistent detoxification. Our data indicates that plays metabolic pyrethroids thus target design new tools combat malaria.