Coordinated P450–UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa
4 affiliations
- 1State Key Laboratory of Cotton Bio-breeding and Integrated Utilization, School of Life Sciences, College of Agriculture, Henan University, Kaifeng, Henan, China
- 2State Key Laboratory of Agricultural and Forestry Biosecurity, Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
- 3School of Wetlands, Yancheng Teachers University, Yancheng, China
- 4Centre for Ecology and Conservation, University of Exeter, Penryn, United Kingdom
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.
The 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.
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BibTeX
@article{wang2026coordinated,
title = {{Coordinated P450–UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa}},
author = {Huidong Wang and Yajie Kong and Xinyue Su and Yu Shi and Jianpeng Zhang and Yinjia Wang and Yajuan Xiao and Xing Geng and Jing Song and Yueru Ye and Kairan Zuo and Chris Bass and Shutang Zhou},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3004013},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004013},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Coordinated P450–UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa
AU - Huidong Wang
AU - Yajie Kong
AU - Xinyue Su
AU - Yu Shi
AU - Jianpeng Zhang
AU - Yinjia Wang
AU - Yajuan Xiao
AU - Xing Geng
AU - Jing Song
AU - Yueru Ye
AU - Kairan Zuo
AU - Chris Bass
AU - Shutang Zhou
PY - 2026
DA - 2026/09/22
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004013
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004013
AB - 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. The 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.
SN - 1545-7885
ER -