Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.
- Yan Y Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA, USA.
- Liu Q Department of Molecular, Cell, and Developmental Biology and Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA, USA.
- Zang X State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
- Yuan S Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Bat-Erdene U Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA, USA.
- Nguyen C Department of Molecular, Cell, and Developmental Biology and Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA, USA.
- Gan J State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, China.
- Zhou J State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. jiahai@mail.sioc.ac.cn.
- Jacobsen SE Department of Molecular, Cell, and Developmental Biology and Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA, USA. jacobsen@ucla.edu.
- Tang Y Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA, USA. yitang@ucla.edu.
- 2018-07-12
Published in:
- Nature. - 2018
Arabidopsis
Biological Products
Enzyme Inhibitors
Herbicide Resistance
Herbicides
Heterocyclic Compounds, 3-Ring
Hydro-Lyases
Models, Molecular
Multigene Family
Plant Growth Regulators
Plants, Genetically Modified
Transgenes
English
Bioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century1-3. The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools4-6. However, compared to traditional bioactivity-guided approaches, genome mining of natural products with specific and potent biological activities remains challenging4. Here we present the discovery and validation of a potent herbicide that targets a critical metabolic enzyme that is required for plant survival. Our approach is based on the co-clustering of a self-resistance gene in the natural-product biosynthesis gene cluster7-9, which provides insight into the potential biological activity of the encoded compound. We targeted dihydroxy-acid dehydratase in the branched-chain amino acid biosynthetic pathway in plants; the last step in this pathway is often targeted for herbicide development10. We show that the fungal sesquiterpenoid aspterric acid, which was discovered using the method described above, is a sub-micromolar inhibitor of dihydroxy-acid dehydratase that is effective as a herbicide in spray applications. The self-resistance gene astD was validated to be insensitive to aspterric acid and was deployed as a transgene in the establishment of plants that are resistant to aspterric acid. This herbicide-resistance gene combination complements the urgent ongoing efforts to overcome weed resistance11. Our discovery demonstrates the potential of using a resistance-gene-directed approach in the discovery of bioactive natural products.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1038/s41586-018-0319-4
- PMID 29995859
- Persistent URL
- https://folia.unifr.ch/global/documents/225981
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