{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:16:28Z","timestamp":1788455788947,"version":"build-2803163510"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100010203","name":"Agriculture Research System of China","doi-asserted-by":"publisher","award":["CARS-24-C-02"],"award-info":[{"award-number":["CARS-24-C-02"]}],"id":[{"id":"10.13039\/501100010203","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013211","name":"Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences","doi-asserted-by":"publisher","award":["Y2023XK15"],"award-info":[{"award-number":["Y2023XK15"]}],"id":[{"id":"10.13039\/501100013211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013211","name":"Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences","doi-asserted-by":"publisher","award":["Y2024XK01"],"award-info":[{"award-number":["Y2024XK01"]}],"id":[{"id":"10.13039\/501100013211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32221004"],"award-info":[{"award-number":["32221004"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32272598"],"award-info":[{"award-number":["32272598"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32361133558"],"award-info":[{"award-number":["32361133558"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neonicotinoid insecticides are widely used to control sap-feeding pests, but their effectiveness is increasingly limited by cytochrome P450-mediated metabolic resistance. Here, we investigated the role of CYP4C64 in nitenpyram (NIT) detoxification in Bemisia tabaci through expression analyses, bioassays, heterologous expression, and in vitro metabolism assays. CYP4C64 was functionally expressed in insect cells using a Bac-to-Bac baculovirus system. UPLC\u2013MS analysis showed that CYP4C64 catalyzed the conversion of NIT to IM-1-4, the major metabolite identified under the experimental conditions, which exhibited substantially lower toxicity than the parent compound. Enzyme kinetic analysis further confirmed the metabolic activity of CYP4C64 toward NIT. These findings provide direct biochemical evidence that CYP4C64 contributes to nitenpyram detoxification in B. tabaci and demonstrate that the Bac-to-Bac expression system is an effective platform for functional characterization of insect P450 enzymes involved in insecticide metabolism.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c02788","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:01:53Z","timestamp":1787151713000},"page":"26992-27001","source":"Crossref","is-referenced-by-count":0,"title":["CYP4C64 Directly\nMetabolizes Nitenpyram to IM-1-4\nConferring Resistance in the Whitefly,\n                    <i>Bemisia tabaci<\/i>"],"prefix":"10.1021","volume":"74","author":[{"given":"Wenhan","family":"Cheng","sequence":"first","affiliation":[{"name":"Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hantang","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Suzhou Plant Quarantine and Protection Station , ,","place":["Suzhou, China, 234000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Suzhou Plant Quarantine and Protection Station , ,","place":["Suzhou, China, 234000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3508-6695","authenticated-orcid":true,"given":"Youjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Ma","sequence":"additional","affiliation":[{"name":"Suzhou Plant Quarantine and Protection Station , ,","place":["Suzhou, China, 234000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8159-6923","authenticated-orcid":true,"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"issue":"5591","key":"2026090311502063900_cit1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1126\/science.1078052","article-title":"An overview of insecticide resistance","volume":"298","author":"Hemingway","year":"2002","journal-title":"Science"},{"key":"2026090311502063900_cit2","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1146\/annurev.en.36.010191.002243","article-title":"Whitefly Biology Annu","volume":"36","author":"Byrne","year":"1991","journal-title":"Rev. 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Generalis"},{"key":"2026090311502063900_cit24","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ibmb.2017.12.006","article-title":"Phylogenetic\nand functional\ncharacterization of ten P450 genes from the CYP6AE subfamily of Helicoverpa\narmigera involved in xenobiotic metabolism","volume":"93","author":"Shi","year":"2018","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"5","key":"2026090311502063900_cit25","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1021\/acs.jafc.2c08353","article-title":"CYP6DW3Metabolizes Imidacloprid to\nImidacloprid-urea in Whitefly\n(Bemisia tabaci)","volume":"71","author":"Xue","year":"2023","journal-title":"J. Agric. Food Chem."},{"issue":"22","key":"2026090311502063900_cit26","doi-asserted-by":"publisher","first-page":"4096","DOI":"10.1002\/jssc.201800612","article-title":"Determination of nitenpyram and 6-chloronicotinic acid in environmental\nsamples by ion chromatography coupled with online photochemically\ninduced fluorescence detector","volume":"41","author":"Muhammad","year":"2018","journal-title":"J. Sep. Sci."},{"issue":"36","key":"2026090311502063900_cit27","doi-asserted-by":"publisher","first-page":"20122","DOI":"10.1021\/acs.jafc.4c06273","article-title":"CYP4CE1Metabolized\nNitenpyram through Two Types of Oxidation Reaction, Hydroxylation,\nand N-Demethylation","volume":"72","author":"Zhang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026090311502063900_cit28","doi-asserted-by":"publisher","first-page":"20120429","DOI":"10.1098\/rstb.2012.0429","article-title":"Role of cytochrome\nP450s in insecticide resistance: impact on the control of mosquito-borne\ndiseases and use of insecticides on Earth","volume":"368","author":"David","year":"2013","journal-title":"Philos.\nTrans. R. Soc. B Biol. Sci."},{"key":"2026090311502063900_cit29","doi-asserted-by":"publisher","first-page":"105468","DOI":"10.1016\/j.pestbp.2023.105468","article-title":"Cytochrome\nP450 CYP6DB3 was involved in thiamethoxam and imidacloprid resistance\nin Bemisia tabaci Q (Hemiptera: Aleyrodidae)","volume":"194","author":"Wei","year":"2023","journal-title":"Pestic. Biochem. Physiol."},{"issue":"10","key":"2026090311502063900_cit30","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.ibmb.2009.08.006","article-title":"Structural\nmodel and functional characterization of the Bemisia tabaci CYP6CM1vQ,\na cytochrome P450 associated with high levels of imidacloprid resistance","volume":"39","author":"Karunker","year":"2009","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"19","key":"2026090311502063900_cit31","doi-asserted-by":"publisher","first-page":"10246","DOI":"10.1073\/pnas.1913603117","article-title":"MAPK-directed activation\nof the whitefly transcription factor CREB leads to P450-mediated imidacloprid\nresistance","volume":"117","author":"Yang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"7","key":"2026090311502063900_cit32","doi-asserted-by":"publisher","first-page":"2923","DOI":"10.1021\/jf102438c","article-title":"Neonicotinoid\nmetabolism: compounds, substituents, pathways, enzymes, organisms,\nand relevance","volume":"59","author":"Casida","year":"2011","journal-title":"J. Agric. Food Chem."},{"issue":"8","key":"2026090311502063900_cit33","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1271\/bbb.69.1442","article-title":"Neonicotinoids\nShow Selective and Diverse Actions on Their Nicotinic Receptor Targets:\nElectrophysiology, Molecular Biology, and Receptor Modeling Studies","volume":"69","author":"Matsuda","year":"2005","journal-title":"Biosci., Biotechnol., Biochem."},{"key":"2026090311502063900_cit34","doi-asserted-by":"publisher","first-page":"1209322","DOI":"10.3389\/fmicb.2023.1209322","article-title":"Nitenpyram biodegradation\nby a novel nitenpyram-degrading bacterium, Ochrobactrum sp. strain\nDF-1, and its novel degradation pathway","volume":"14","author":"Wang","year":"2023","journal-title":"Front.\nMicrobiol."},{"issue":"6","key":"2026090311502063900_cit35","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1021\/tx0002583","article-title":"Common\nand uncommon cytochrome P450 reactions related to metabolism and chemical\ntoxicity","volume":"14","author":"Guengerich","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"2026090311502063900_cit36","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1021\/tx0200360","article-title":"Neonicotinoid Insecticides: Reduction\nand Cleavage of Imidacloprid Nitroimine Substituent by Liver Microsomal\nand Cytosolic Enzymes","volume":"15","author":"Schulz-Jander","year":"2002","journal-title":"Chem. Res. Toxicol."},{"issue":"1","key":"2026090311502063900_cit37","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1021\/tx700079z","article-title":"Cytochrome\nP450 and chemical toxicology","volume":"21","author":"Guengerich","year":"2008","journal-title":"Chem. Res. Toxicol."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c02788","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/34\/26992\/66881803\/acs.jafc.6c02788.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/34\/26992\/66881803\/acs.jafc.6c02788.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:24:37Z","timestamp":1788452677000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/34\/26992\/5276875\/CYP4C64-Directly-Metabolizes-Nitenpyram-to-IM-1-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":37,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,19]]},"published-print":{"date-parts":[[2026,9,2]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c02788","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}