{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:55:40Z","timestamp":1788807340930,"version":"build-2803163510"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Insect Biochemistry and Molecular Biology"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1016\/j.ibmb.2022.103813","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T22:30:34Z","timestamp":1658356234000},"page":"103813","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Sequential phase I metabolism of pyrethroids by duplicated CYP6P9 variants results in the loss of the terminal benzene moiety and determines resistance in the malaria mosquito Anopheles funestus"],"prefix":"10.1016","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4881-8114","authenticated-orcid":false,"given":"Melanie","family":"Nolden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.I.","family":"Paine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7525-8589","authenticated-orcid":false,"given":"Ralf","family":"Nauen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ibmb.2022.103813_bib1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/jee\/18.2.265a","article-title":"A method of computing the effectiveness of an insecticide","volume":"18","author":"Abbott","year":"1925","journal-title":"J. Econ. Entomol."},{"key":"10.1016\/j.ibmb.2022.103813_bib2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2583.2008.00776.x","article-title":"Over expression of a cytochrome P450 (CYP6P9) in a major african malaria vector","volume":"17","author":"Amenya","year":"2008","journal-title":"Insect Mol. Biol."},{"key":"10.1016\/j.ibmb.2022.103813_bib3","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature15535","article-title":"The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015","volume":"526","author":"Bhatt","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ibmb.2022.103813_bib4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1079\/BER2001108","article-title":"Bioassay and biochemical analyses of insecticide resistance in southern African Anopheles funestus (Diptera: Culicidae)","volume":"91","author":"Brooke","year":"2001","journal-title":"Bull. Entomol. Res."},{"key":"10.1016\/j.ibmb.2022.103813_bib5","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev.pa.23.040183.002213","article-title":"Mechanism of selective action of pyrethroid","author":"Casida","year":"1983","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.ibmb.2022.103813_bib6","doi-asserted-by":"crossref","first-page":"8855","DOI":"10.1073\/pnas.0709249105","article-title":"Comparative molecular modeling of Anopheles gambiae CYP6Z1, a mosquito P450 capable of metabolizing DDT","volume":"105","author":"Chiu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ibmb.2022.103813_bib7","doi-asserted-by":"crossref","DOI":"10.3791\/221","article-title":"Protocol for mosquito rearing (A. gambiae)","author":"Das","year":"2007","journal-title":"JoVE"},{"key":"10.1016\/j.ibmb.2022.103813_bib8","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2012.0429","article-title":"Role of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth","author":"David","year":"2013","journal-title":"Philos. Trans. R. Soc. B."},{"key":"10.1016\/j.ibmb.2022.103813_bib9","series-title":"Insect CYP Genes and P450 Enzymes, Reference Module in Life Sciences","author":"Feyereisen","year":"2019"},{"key":"10.1016\/j.ibmb.2022.103813_bib10","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD012776.pub2","article-title":"Piperonyl butoxide (PBO) combined with pyrethroids in long-lasting insecticidal nets (LLINs) to prevent malaria in Africa","author":"Gleave","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.ibmb.2022.103813_bib11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0021-9258(18)48462-1","article-title":"Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences","volume":"267","author":"Gotoh","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ibmb.2022.103813_bib12","article-title":"A mechanism\u2010based approach unveils metabolic routes potentially mediating chlorantraniliprole synergism in honey bees, Apis mellifera L., by azole fungicides","author":"Haas","year":"2021","journal-title":"Pest Manag. Sci."},{"key":"10.1016\/j.ibmb.2022.103813_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2020.106372","article-title":"Pesticide risk assessment at the molecular level using honey bee cytochrome P450 enzymes : a complementary approach","volume":"147","author":"Haas","year":"2021","journal-title":"Environ. Int."},{"key":"10.1016\/j.ibmb.2022.103813_bib14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.pestbp.2019.05.011","article-title":"Differential metabolism of imidacloprid and dinotefuran by Bemisia tabaci CYP6CM1 variants","volume":"159","author":"Hamada","year":"2019","journal-title":"Pestic. Biochem. Physiol."},{"key":"10.1016\/j.ibmb.2022.103813_bib15","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1021\/bi00128a009","article-title":"Site-directed mutagenesis of cytochrome P450s CYP2A1 and CYP2A2: influence of the distal helix on the kinetics of testosterone hydroxylation","volume":"31","author":"Hanioka","year":"1992","journal-title":"Biochem."},{"key":"10.1016\/j.ibmb.2022.103813_bib16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/00498254.2018.1474283","article-title":"Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes","volume":"49","author":"Hedges","year":"2019","journal-title":"Xenobiotica"},{"key":"10.1016\/j.ibmb.2022.103813_bib17","doi-asserted-by":"crossref","DOI":"10.1006\/abbi.1994.1184","article-title":"Differential roles of Glu318 and Thr319 in cytochrome P450 1A2 catalysis supported by NADPH-cytochrome P450 reductase and tert-butyl hydroperoxide","author":"Hiroya","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ibmb.2022.103813_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0149738","article-title":"Contact bioassays with phenoxybenzyl and tetrafluorobenzyl pyrethroids against target-site and metabolic resistant mosquitoes","volume":"11","author":"Horstmann","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.ibmb.2022.103813_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/genes9030140","article-title":"Pyrethroid resistance in the major malaria vector anopheles funestus is exacerbated by overexpression and overactivity of the P450 CYP6AA1 across Africa","volume":"9","author":"Ibrahim","year":"2018","journal-title":"Genes"},{"key":"10.1016\/j.ibmb.2022.103813_bib20","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1111\/mec.13673","article-title":"The P450 CYP6Z1 confers carbamate\/pyrethroid cross-resistance in a major African malaria vector beside a novel carbamate-insensitive N485I acetylcholinesterase-1 mutation","volume":"25","author":"Ibrahim","year":"2016","journal-title":"Mol. Ecol."},{"key":"10.1016\/j.ibmb.2022.103813_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005618","article-title":"Allelic variation of cytochrome P450s drives resistance to bednet insecticides in a major malaria vector","volume":"11","author":"Ibrahim","year":"2015","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ibmb.2022.103813_bib22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12863-017-0539-x","article-title":"Investigating knockdown resistance (kdr) mechanism against pyrethroids\/DDT in the malaria vector Anopheles funestus across Africa","volume":"18","author":"Irving","year":"2017","journal-title":"BMC Genet."},{"key":"10.1016\/j.ibmb.2022.103813_bib23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1365-2583.1998.72062.x","article-title":"Molecular characterization of pyrethroid knockdown resistance (kdr) in the major malaria vector Anopheles gambiae s.s","volume":"7","author":"Martinez-Torres","year":"1998","journal-title":"Insect Mol. Biol."},{"key":"10.1016\/j.ibmb.2022.103813_bib24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13071-021-04609-5","article-title":"Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations","volume":"14","author":"Moyes","year":"2021","journal-title":"Parasites Vectors"},{"key":"10.1016\/j.ibmb.2022.103813_bib25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev-ento-070621-061328","article-title":"The role of cytochrome P450s in insect toxicology and resistance","volume":"67","author":"Nauen","year":"2022","journal-title":"Annu. Rev. Entomol."},{"key":"10.1016\/j.ibmb.2022.103813_bib26","article-title":"Towards understanding transfl uthrin efficacy in a pyrethroid-resistant strain of the malaria vector Anopheles funestus with special reference to cytochrome P450-mediated detoxification","volume":"1","author":"Nolden","year":"2021","journal-title":"Curr. Res. Parasitol. Vector-Borne Dis."},{"key":"10.1016\/j.ibmb.2022.103813_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.pestbp.2022.105051","article-title":"Biochemical profiling of functionally expressed CYP6P9 variants of the malaria vector Anopheles funestus with special reference to cytochrome b5 and its role in pyrethroid and coumarin substrate metabolism","volume":"182","author":"Nolden","year":"2022","journal-title":"Pestic. Biochem. Physiol."},{"key":"10.1016\/j.ibmb.2022.103813_bib28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"Software news and update AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Oleg","year":"2010","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ibmb.2022.103813_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/S0021-9258(20)82245-5","article-title":"The carbon monoxide-binding pigment of liver microsomes","volume":"239","author":"Omura","year":"1964","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ibmb.2022.103813_bib30","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1074\/jbc.M209519200","article-title":"Residues glutamate 216 and aspartate 301 are key determinants of substrate specificity and product regioselectivity in cytochrome P450 2D6","volume":"278","author":"Paine","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ibmb.2022.103813_bib31","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(18)30427-6","article-title":"Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two fact","volume":"391","author":"Protopopoff","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.ibmb.2022.103813_bib32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.pt.2010.08.004","article-title":"Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?","volume":"27","author":"Ranson","year":"2011","journal-title":"Trends Parasitol."},{"key":"10.1016\/j.ibmb.2022.103813_bib33","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1186\/1471-2164-15-817","article-title":"The highly polymorphic CYP6M7 cytochrome P450 gene partners with the directionally selected CYP6P9a and CYP6P9b genes to expand the pyrethroid resistance front in the malaria vector Anopheles funestus in Africa","volume":"15","author":"Riveron","year":"2014","journal-title":"BMC Genom."},{"key":"10.1016\/j.ibmb.2022.103813_bib34","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1073\/pnas.1216705110","article-title":"Directionally selected cytochrome P450 alleles are driving the spread of pyrethroid resistance in the major malaria vector Anopheles funestus","volume":"110","author":"Riveron","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ibmb.2022.103813_bib35","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1021\/jf60218a060","article-title":"Decamethrin metabolism in rats","volume":"26","author":"Ruzo","year":"1978","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.ibmb.2022.103813_bib36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1124\/dmd.108.022343","article-title":"In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome P450 isoforms","volume":"37","author":"Scollon","year":"2009","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ibmb.2022.103813_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.ibmb.2020.103486","article-title":"Roles of the variable P450 substrate recognition sites SRS1 and SRS6 in esfenvalerate metabolism by CYP6AE subfamily enzymes in Helicoverpa armigera","volume":"127","author":"Shi","year":"2020","journal-title":"Insect Biochem. Mol. Biol."},{"key":"10.1016\/j.ibmb.2022.103813_bib38","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1021\/jf60222a059","article-title":"Metabolism of trans-and cis-Permethrin, trans-and cis-Cypermethrin, and Decamethrin by Microsomal Enzymes","volume":"27","author":"Shono","year":"1979","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.ibmb.2022.103813_bib39","series-title":"Neurotoxicity of Pesticides","first-page":"113","article-title":"Neurotoxicology of pyrethroid insecticides","author":"Soderlund","year":"2020"},{"key":"10.1016\/j.ibmb.2022.103813_bib40","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.ibmb.2011.02.003","article-title":"Cytochrome P450 6M2 from the malaria vector Anopheles gambiae metabolizes pyrethroids: sequential metabolism of deltamethrin revealed","volume":"41","author":"Stevenson","year":"2011","journal-title":"Insect Biochem. Mol. Biol."},{"key":"10.1016\/j.ibmb.2022.103813_bib41","series-title":"World Malaria Report","year":"2021"},{"key":"10.1016\/j.ibmb.2022.103813_bib42","series-title":"World Malaria Report 2020","year":"2020"},{"key":"10.1016\/j.ibmb.2022.103813_bib43","series-title":"Global Report on Insecticide Resistance in Malaria Vectors: 2010-2016","year":"2018"},{"key":"10.1016\/j.ibmb.2022.103813_bib44","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1186\/s13071-019-3774-3","article-title":"Characterisation of Anopheles strains used for laboratory screening of new vector control products","volume":"12","author":"Williams","year":"2019","journal-title":"Parasites Vectors"},{"key":"10.1016\/j.ibmb.2022.103813_bib45","article-title":"RNAseq-based gene expression profiling of the Anopheles funestus pyrethroid-resistant strain FUMOZ highlights the predominant role of the duplicated CYP6P9a\/b cytochrome P450s","volume":"12","author":"Wondji","year":"2022","journal-title":"G3 Genes Genomes Genet."},{"key":"10.1016\/j.ibmb.2022.103813_bib46","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.pestbp.2019.06.007","article-title":"Cross-resistance profiles of malaria mosquito P450s associated with pyrethroid resistance against WHO insecticides","volume":"161","author":"Yunta","year":"2019","journal-title":"Pestic. Biochem. Physiol."},{"key":"10.1016\/j.ibmb.2022.103813_bib47","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ibmb.2013.11.008","article-title":"Molecular and functional characterization of CYP6BQ23, a cytochrome P450 conferring resistance to pyrethroids in European populations of pollen beetle, Meligethes aeneus","volume":"45","author":"Zimmer","year":"2014","journal-title":"Insect Biochem. Mol. Biol."},{"key":"10.1016\/j.ibmb.2022.103813_bib48","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.cub.2017.11.060","article-title":"Neofunctionalization of duplicated P450 genes drives the evolution of insecticide resistance in the Brown planthopper","volume":"28","author":"Zimmer","year":"2018","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ibmb.2022.103813_bib49","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.pestbp.2011.04.011","article-title":"Cytochrome P450 mediated pyrethroid resistance in European populations of Meligethes aeneus (Coleoptera: nitidulidae)","volume":"100","author":"Zimmer","year":"2011","journal-title":"Pestic. Biochem. Physiol."}],"container-title":["Insect Biochemistry and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0965174822000959?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0965174822000959?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T16:49:33Z","timestamp":1760806173000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0965174822000959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":49,"alternative-id":["S0965174822000959"],"URL":"https:\/\/doi.org\/10.1016\/j.ibmb.2022.103813","relation":{},"ISSN":["0965-1748"],"issn-type":[{"value":"0965-1748","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sequential phase I metabolism of pyrethroids by duplicated CYP6P9 variants results in the loss of the terminal benzene moiety and determines resistance in the malaria mosquito Anopheles funestus","name":"articletitle","label":"Article Title"},{"value":"Insect Biochemistry and Molecular Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ibmb.2022.103813","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"103813"}}