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<p>Herbicides in combination with genetically modified herbicide-resistant crops have revolutionized modern weed management, increased crop yields, and facilitated farming practices. However, rapid evolution of herbicide-resistant weeds necessitates new resistance traits to sustain control efficacy. Here, we introduce a terminal carboxyl anchoring mechanism-inspired approach for precise discovery of P450 herbicide resistance genes, by which a number of bacterial P450 peroxygenases are predicted and confirmed to degrade auxin herbicides. Upon enzyme engineering, the optimal mutant P450<sub>BSβ</sub>-F46A can efficiently degrade diverse auxin herbicides and other carboxyl-containing herbicides. Mechanistic studies reveal that Compound I-mediated hydroxylation initiates the C‒O bond cleavage, followed by aromatic ring hydroxylation, thus forming a unique two-step degradation pathway. Transgenic rice expressing <i>P450</i><sub><i>BSβ</i></sub><i>-F46A-CPR</i> confers significant resistance to a recently commercialized auxin herbicide fluchloraminopyr. This work demonstrates the potential of the mechanism-driven strategy in directed discovery of broad-spectrum resistance genes for herbicide-resistant crop engineering.</p>

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Anchoring mechanism-inspired discovery of a bacterial P450 gene conferring resistance to auxin herbicides

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月25日

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  • Yuanyuan Jiang,
  • Junjie Zhang,
  • Zhong Li,
  • Lingyan Wang,
  • Yuyu Guo,
  • Yuxuan Li,
  • Xisong Feng,
  • Wen Gao,
  • Yong Li,
  • Zijia Li,
  • Jieke Du,
  • Guoqiang Zhang,
  • Piqian Gong,
  • Wenhan Fang,
  • Xiang Gao,
  • Mingyi Bai,
  • Frank Hollmann,
  • Mei Zhang,
  • He Huang,
  • Binju Wang,
  • Sudong Mo,
  • Huarong Li,
  • Wei Peng,
  • Shengying Li

摘要

Herbicides in combination with genetically modified herbicide-resistant crops have revolutionized modern weed management, increased crop yields, and facilitated farming practices. However, rapid evolution of herbicide-resistant weeds necessitates new resistance traits to sustain control efficacy. Here, we introduce a terminal carboxyl anchoring mechanism-inspired approach for precise discovery of P450 herbicide resistance genes, by which a number of bacterial P450 peroxygenases are predicted and confirmed to degrade auxin herbicides. Upon enzyme engineering, the optimal mutant P450BSβ-F46A can efficiently degrade diverse auxin herbicides and other carboxyl-containing herbicides. Mechanistic studies reveal that Compound I-mediated hydroxylation initiates the C‒O bond cleavage, followed by aromatic ring hydroxylation, thus forming a unique two-step degradation pathway. Transgenic rice expressing P450BSβ-F46A-CPR confers significant resistance to a recently commercialized auxin herbicide fluchloraminopyr. This work demonstrates the potential of the mechanism-driven strategy in directed discovery of broad-spectrum resistance genes for herbicide-resistant crop engineering.