{
  "abstract": "Plants and herbivorous insects are engaged in a continuous evolutionary arms race driven by chemical defences and counter-defences. How insects integrate distinct detoxification systems to overcome diverse phytochemicals, and how such mechanisms contribute to host-range divergence, remains poorly understood. Here, we uncover a cooperative cytochrome P450–UDP-glycosyltransferase (UGT) cascade that mediates furanocoumarin tolerance in Helicoverpa armigera. Comparative genomic analyses across Helicoverpa and related noctuid species revealed that the UGT33 family is the most extensively expanded and dynamically diversified UGT lineage in Helicoverpa. Targeted CRISPR–Cas9 knockouts of UGT33 gene clusters in polyphagous H. armigera demonstrated their essential roles in detoxifying the furanocoumarins xanthotoxin and imperatorin. Combined metabolic and functional assays further established a sequential detoxification pathway, in which the cytochrome P450 CYP6AE19 catalyses either the O-dealkylation of xanthotoxin to yield xanthotoxol or the aromatic-carbon hydroxylation of xanthotoxin to form 5-hydroxyxanthotoxin, which are subsequently glycosylated by UGT33 enzymes to form their less-toxic glucosides. In contrast, impaired CYP6AE19–UGT33 coordination in the oligophagous Helicoverpa assulta was associated with reduced xanthotoxin detoxification and high sensitivity to this compound. Together, these findings provide direct evidence for coordinated Phase I–Phase II detoxification of a plant defensive compound in insects and show that functional divergence in this pathway contributes to interspecific differences in plant toxin tolerance, which are associated with contrasting dietary breadth in closely related herbivorous insects.\n\nThe mechanisms by which herbivorous insects coordinate detoxification pathways to counter plant defences and diversify host use remain unclear. This study shows that a cooperative CYP6AE19-UGT33 pathway drives furanocoumarin detoxification in Helicoverpa, highlighting a molecular basis for variation in toxin tolerance and host range.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Cotton Bio-breeding and Integrated Utilization, School of Life Sciences, College of Agriculture, Henan University, Kaifeng, Henan, China",
    "State Key Laboratory of Agricultural and Forestry Biosecurity, Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China",
    "School of Wetlands, Yancheng Teachers University, Yancheng, China",
    "Centre for Ecology and Conservation, University of Exeter, Penryn, United Kingdom"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huidong Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yajie Kong"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinyue Su"
    },
    {
      "affs": [
        3
      ],
      "name": "Yu Shi"
    },
    {
      "name": "Jianpeng Zhang"
    },
    {
      "name": "Yinjia Wang"
    },
    {
      "name": "Yajuan Xiao"
    },
    {
      "name": "Xing Geng"
    },
    {
      "name": "Jing Song"
    },
    {
      "name": "Yueru Ye"
    },
    {
      "name": "Kairan Zuo"
    },
    {
      "name": "Chris Bass"
    },
    {
      "name": "Shutang Zhou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8t1sch87bdv0w.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pbio.3004013",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004013",
  "id": "8t1sch87bdv0w",
  "issns": [
    "1545-7885"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004013",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1109|Insect-Plant Interactions and Control"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzyme chemistry/Enzyme metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Enzymes"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Recombinant proteins"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Life cycles/Larvae"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Nutrition/Diet"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Animals/Invertebrates/Arthropoda/Insects"
    ],
    [
      "plos",
      "/Biology and life sciences/Toxicology/Detoxification"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animals/Invertebrates/Arthropoda/Insects"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Entomology/Insects"
    ],
    [
      "plos",
      "/Medicine and health sciences/Nutrition/Diet"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Detoxification"
    ]
  ],
  "openalex": "W7214029196",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3004013&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/8t1sch87bdv0w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pbio.3004013",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004013"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:enzymology",
      "subfield": "enzymology-metabolism"
    },
    {
      "field": "medicine",
      "origin": "plos:nutrition",
      "subfield": "nutrition"
    },
    {
      "field": "medicine",
      "origin": "plos:toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Coordinated P450–UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa",
  "title_text": "Coordinated P450–UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/8t1sch87bdv0w",
  "venue": "PLOS Biology",
  "versions": []
}