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A fungal tolerance trait and selective inhibitors proffer HMG-CoA reductase as a herbicide mode-of-action

Author

Listed:
  • Joel Haywood

    (Curtin University, Bentley
    The University of Western Australia)

  • Karen J. Breese

    (The University of Western Australia)

  • Jingjing Zhang

    (The University of Western Australia)

  • Mark T. Waters

    (The University of Western Australia)

  • Charles S. Bond

    (The University of Western Australia)

  • Keith A. Stubbs

    (The University of Western Australia)

  • Joshua S. Mylne

    (Curtin University, Bentley
    The University of Western Australia)

Abstract

Decades of intense herbicide use has led to resistance in weeds. Without innovative weed management practices and new herbicidal modes of action, the unabated rise of herbicide resistance will undoubtedly place further stress upon food security. HMGR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) is the rate limiting enzyme of the eukaryotic mevalonate pathway successfully targeted by statins to treat hypercholesterolemia in humans. As HMGR inhibitors have been shown to be herbicidal, HMGR could represent a mode of action target for the development of herbicides. Here, we present the crystal structure of a HMGR from Arabidopsis thaliana (AtHMG1) which exhibits a wider active site than previously determined structures from different species. This plant conserved feature enables the rational design of specific HMGR inhibitors and we develop a tolerance trait through sequence analysis of fungal gene clusters. These results suggest HMGR to be a viable herbicide target modifiable to provide a tolerance trait.

Suggested Citation

  • Joel Haywood & Karen J. Breese & Jingjing Zhang & Mark T. Waters & Charles S. Bond & Keith A. Stubbs & Joshua S. Mylne, 2022. "A fungal tolerance trait and selective inhibitors proffer HMG-CoA reductase as a herbicide mode-of-action," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33185-0
    DOI: 10.1038/s41467-022-33185-0
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    References listed on IDEAS

    as
    1. Yan Yan & Qikun Liu & Xin Zang & Shuguang Yuan & Undramaa Bat-Erdene & Calvin Nguyen & Jianhua Gan & Jiahai Zhou & Steven E. Jacobsen & Yi Tang, 2018. "Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action," Nature, Nature, vol. 559(7714), pages 415-418, July.
    2. Shi-You Jiang & Hui Li & Jing-Jie Tang & Jie Wang & Jie Luo & Bing Liu & Jin-Kai Wang & Xiong-Jie Shi & Hai-Wei Cui & Jie Tang & Fan Yang & Wei Qi & Wen-Wei Qiu & Bao-Liang Song, 2018. "Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    3. Roger E. Summons & Linda L. Jahnke & Janet M. Hope & Graham A. Logan, 1999. "2-Methylhopanoids as biomarkers for cyanobacterial oxygenic photosynthesis," Nature, Nature, vol. 400(6744), pages 554-557, August.
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