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Pyrazinamide and derivatives block ethylene biosynthesis by inhibiting ACC oxidase

Author

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  • Xiangzhong Sun

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    Academy for Advanced Interdisciplinary Studies, Peking University
    Peking-Tsinghua Center for Life Sciences
    Southern University of Science and Technology)

  • Yaxin Li

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University)

  • Wenrong He

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    Center for Plant Cell Biology, University of California)

  • Chenggong Ji

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University)

  • Peixue Xia

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    Academy for Advanced Interdisciplinary Studies, Peking University
    Peking-Tsinghua Center for Life Sciences)

  • Yichuan Wang

    (Southern University of Science and Technology)

  • Shuo Du

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University)

  • Hongjiang Li

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    Center for Plant Cell Biology, University of California)

  • Natasha Raikhel

    (Center for Plant Cell Biology, University of California)

  • Junyu Xiao

    (The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    Peking-Tsinghua Center for Life Sciences)

  • Hongwei Guo

    (Peking-Tsinghua Center for Life Sciences
    Southern University of Science and Technology)

Abstract

Ethylene is an important phytohormone that promotes the ripening of fruits and senescence of flowers thereby reducing their shelf lives. Specific ethylene biosynthesis inhibitors would help to decrease postharvest loss. Here, we identify pyrazinamide (PZA), a clinical drug used to treat tuberculosis, as an inhibitor of ethylene biosynthesis in Arabidopsis thaliana, using a chemical genetics approach. PZA is converted to pyrazinecarboxylic acid (POA) in plant cells, suppressing the activity of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), the enzyme catalysing the final step of ethylene formation. The crystal structures of Arabidopsis ACO2 in complex with POA or 2-Picolinic Acid (2-PA), a POA-related compound, reveal that POA/2-PA bind at the active site of ACO, preventing the enzyme from interacting with its natural substrates. Our work suggests that PZA and its derivatives may be promising regulators of plant metabolism, in particular ethylene biosynthesis.

Suggested Citation

  • Xiangzhong Sun & Yaxin Li & Wenrong He & Chenggong Ji & Peixue Xia & Yichuan Wang & Shuo Du & Hongjiang Li & Natasha Raikhel & Junyu Xiao & Hongwei Guo, 2017. "Pyrazinamide and derivatives block ethylene biosynthesis by inhibiting ACC oxidase," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15758
    DOI: 10.1038/ncomms15758
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