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Cited by 29Plant Molecular Biology ResearchPlant biochemistry and biosynthesisPlant Parasitism and Resistance

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Chemical genetic screening identifies nalacin as an inhibitor of GH3 amido synthetase for auxin conjugation

Open access
Xie, Yinpeng, Zhu, Ying, Wang, Na, Luo, Min, Ota, Tsuyoshi, Guo, Ruipan, Takahashi, Ikuo, Yu, Zongjun, Aizezi, Yalikunjiang, Zhang, Linlin, Yan, Yan, Zhang, Yujie, Bao, Hongyu, Wang, Yichuan, Zhu, Ziqiang, Huang, Ancheng C., Zhao, Yunde, Asami, Tadao, Huang, Hongda, Guo, Hongwei, Jiang, Kai·2022·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2209256119PMC PMC9894192

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Abstract

Auxin inactivation is critical for plant growth and development. To develop plant growth regulators functioning in auxin inactivation pathway, we performed a phenotype-based chemical screen in Arabidopsis and identified a chemical, nalacin, that partially mimicked the effects of auxin. Genetic, pharmacological, and biochemical approaches demonstrated that nalacin exerts its auxin-like activities by inhibiting indole-3-acetic acid (IAA) conjugation that is mediated by Gretchen Hagen 3 (GH3) acyl acid amido synthetases. The crystal structure of Arabidopsis GH3.6 in complex with D4 (a derivative of nalacin) together with docking simulation analysis revealed the molecular basis of the inhibition of group II GH3 by nalacin. Sequence alignment analysis indicated broad bioactivities of nalacin and D4 as inhibitors of GH3s in vascular plants, which were confirmed, at least, in tomato and rice. In summary, our work identifies nalacin as a potent inhibitor of IAA conjugation mediated by group II GH3 that plays versatile roles in hormone-regulated plant development and has potential applications in both basic research and agriculture.

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Metadata

Authors
Xie, Y., Zhu, Y., Wang, N., Luo, M., Ota, T., Guo, R., Takahashi, I., Yu, Z., Aizezi, Y., Zhang, L., Yan, Y., Zhang, Y., Bao, H., Wang, Y., Zhu, Z., Huang, A. C., Zhao, Y., Asami, T., Huang, H., Guo, H., & Jiang, K.
Affiliations
  • Southern University of Science and Technology (CN)
  • The University of Tokyo (JP)
  • University of California San Diego (US)
  • Nanjing Normal University (CN)
Corresponding author
  • Huang, Hongda
  • Guo, Hongwei
  • Jiang, Kai
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2022-12
Volume
119
Issue
49
Pages
e2209256119-e2209256119
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2209256119
PMC
PMC9894192
OpenAlex
W4310493719
Cited by
29
References
2
Citations by year
2026: 5 · 2025: 13 · 2024: 6 · 2023: 4 · 2022: 1
FWCI
3.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
  • National Natural Science Foundation of China (31911540070, 21907049)
  • MOST | National Key Research and Development Program of China (2019YFA0903904)
  • JSPS Grant-in-Aid for Scientific Research (18H05266)
  • Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes (2019KSYS006)
  • Guanddong Innovative and Entrepreneurial Research Team Program (2016ZT06S172)
  • Shenzhen Science and Technology Program (KYTDPT20181011104005, KQTD20190929173906742)
  • China Postdoctoral Science Foundation (2020M672406)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Parasitism and Resistance
Keywords
auxin conjugation, indole-3-acetic acid, plant growth regulators, chemical genetic screening, Arabidopsis thaliana, enzyme inhibition, tomato, rice
MeSH terms
Genetic Testing, Indoleacetic Acids, Ligases, Plant Growth Regulators, Arabidopsis, Chemical Phenomena

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