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

Agri and Aquaculture

Journal of Aquaculture Research & Development

Author(s): Stevenson BJ, Bibby J, Pignatelli P, Muangnoicharoen S, ONeill PM,

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Abstract Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is a major threat to malaria control programmes. Cytochome P450-mediated detoxification is an important resistance mechanism. CYP6M2 is over-expressed in wild populations of permethrin resistant A. gambiae but its role in detoxification is not clear. CYP6M2 was expressed in Escherichia coli and a structural model was produced to examine its role in pyrethroid metabolism. Both permethrin and deltamethrin were metabolized. Rates were enhanced by A. gambiae cytochrome b(5) with kinetic parameters of K(M)=11±1μM and k(cat)=6.1±0.4 per min for permethrin (1:1 cis-trans) and K(M)=2.0±0.3μM and k(cat)=1.2±0.1 per min for deltamethrin. Mass spectrometry and NMR analysis identified 4'-hydroxy deltamethrin and hydroxymethyl deltamethrin as major and minor deltamethrin metabolites respectively. Secondary breakdown products included cyano(3-hydroxyphenyl)methyl deltamethrate and deltamethric acid. CYP6M2 was most highly transcribed in the midgut and Malpighian tubules of adult A. gambiae, consistent with a role in detoxification. Our data indicates that CYP6M2 plays an important role in metabolic resistance to pyrethroids and thus an important target for the design of new tools to combat malaria. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved. This article was published in Insect Biochem Mol Biol and referenced in Journal of Aquaculture Research & Development

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