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Peer-reviewedCC BY-NCScience Advances

Insect-specific aldehyde synthase governs cuticle strength: a selective insecticide target

  • Yi Ding1
  • Xue Hu1
  • Zihan Pang1
  • Huan Liu1
  • Loushi Shen1
  • Yingqian Liu2
  • Tian Liu1
  1. 1MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology; Dalian, 116024, China.
  2. 2School of Pharmacy, Lanzhou University; Lanzhou, 730000, China.
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Abstract

Cuticular sclerotization is crucial for insect adaptation and flight, historically thought to be dominantly driven by dopamine and its downstream products. In this study, we demonstrate that 3,4-dihydroxyphenylacetaldehyde (DHPAA)-produced by DHPAA synthase (DHPAAS) and known in humans as a toxic dopamine metabolite-plays a central role. Cross-species RNAi, mechanical testing, and precursor quantification, consistently support this conclusion. In the migratory locust, we further reveal that DHPAA is essential for cuticular mechanical properties, whereas dopamine primarily regulates pigmentation. These findings establish a new paradigm for the chemistry of insect cuticle sclerotization. Then, we elucidate the catalytic mechanism of DHPAAS, laying the groundwork for its application in biosynthesis. Furthermore, we identify 2,5,2',4'-tetrahydroxychalcone as a selective inhibitor of DHPAAS. Given that DHPAAS is insect-specific and absent in non-insect arthropods and vertebrates, our work points to a promising strategy for developing selective insecticides.

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Cite

BibTeXRIS
BibTeX
@article{ding2026insectspecific,
  title = {{Insect-specific aldehyde synthase governs cuticle strength: a selective insecticide target}},
  author = {Yi Ding and Xue Hu and Zihan Pang and Huan Liu and Loushi Shen and Yingqian Liu and Tian Liu},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh0368},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh0368},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Insect-specific aldehyde synthase governs cuticle strength: a selective insecticide target
AU  - Yi Ding
AU  - Xue Hu
AU  - Zihan Pang
AU  - Huan Liu
AU  - Loushi Shen
AU  - Yingqian Liu
AU  - Tian Liu
PY  - 2026
DA  - 2026/10/09
JO  - Science Advances
DO  - 10.1126/sciadv.aeh0368
UR  - https://www.science.org/doi/10.1126/sciadv.aeh0368
AB  - Cuticular sclerotization is crucial for insect adaptation and flight, historically thought to be dominantly driven by dopamine and its downstream products. In this study, we demonstrate that 3,4-dihydroxyphenylacetaldehyde (DHPAA)-produced by DHPAA synthase (DHPAAS) and known in humans as a toxic dopamine metabolite-plays a central role. Cross-species RNAi, mechanical testing, and precursor quantification, consistently support this conclusion. In the migratory locust, we further reveal that DHPAA is essential for cuticular mechanical properties, whereas dopamine primarily regulates pigmentation. These findings establish a new paradigm for the chemistry of insect cuticle sclerotization. Then, we elucidate the catalytic mechanism of DHPAAS, laying the groundwork for its application in biosynthesis. Furthermore, we identify 2,5,2',4'-tetrahydroxychalcone as a selective inhibitor of DHPAAS. Given that DHPAAS is insect-specific and absent in non-insect arthropods and vertebrates, our work points to a promising strategy for developing selective insecticides.
SN  - 2375-2548
ER  -