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

IF 13.9 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2026-10-09 DOI:10.1126/sciadv.aeh0368

Yi Ding, Xue Hu, Zihan Pang, Huan Liu, Loushi Shen, Yingqian Liu, Tian Liu

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引用次数: 0

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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昆虫特异性醛合酶控制角质层强度：一种选择性杀虫剂靶标

角质层硬化对昆虫适应和飞行至关重要，历史上认为主要由多巴胺及其下游产物驱动。在这项研究中，我们证明了3,4-二羟基苯乙醛（DHPAA）——由DHPAA合成酶（DHPAAS）产生，在人类中被称为有毒的多巴胺代谢物——起着核心作用。跨物种RNAi，机械测试和前体定量一致支持这一结论。在迁徙蝗虫中，我们进一步发现DHPAA对表皮力学特性至关重要，而多巴胺主要调节色素沉着。这些发现为昆虫角质层硬化的化学研究建立了新的范式。在此基础上，阐述了DHPAAS的催化机理，为其在生物合成中的应用奠定了基础。此外，我们发现2,5,2 ',4 ' -四羟基查尔酮是DHPAAS的选择性抑制剂。鉴于DHPAAS是昆虫特异性的，并且在非昆虫节肢动物和脊椎动物中不存在，我们的工作指出了开发选择性杀虫剂的有希望的策略。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.