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  3. Discovery of DNA Gyrase as a Promising Target against Phytopathogenic Bacteria

Discovery of DNA Gyrase as a Promising Target against Phytopathogenic Bacteria

  • J Agric Food Chem. 2025 Dec 23. doi: 10.1021/acs.jafc.5c13698.
Zhiyan Wang 1 2,  Congting Gao 3,  Rajamanikandan Sundarraj 2,  Dongxiao Shi 3,  Zhe Ni 3,  Jun-An Ma 4,  Xiangjing Wang 3,  Wensheng Xiang 3 5,  Zhiguang Yuchi 1 2,  Chongxi Liu 3
Affiliations

Affiliations

  • 1 Department of Molecular Pharmacology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
  • 2 State Key Laboratory of Synthetic Biology; Frontiers Science Center for Synthetic Biology; Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency; School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China.
  • 3 Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China.
  • 4 Department of Chemistry, State Key Laboratory Synthetic Biology, Tianjin University, Tianjin 300072, China.
  • 5 State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
PMID: 41436099 DOI: 10.1021/acs.jafc.5c13698
Abstract

The growing resistance of phytopathogenic bacteria highlights the need for new bactericides. DNA gyrase, essential in bacteria but absent in Plants and Animals, is an underexploited target for agricultural bactericides. Here, we modeled the Ralstonia solanacearum GyrA-GyrB-DNA complex using AlphaFold3 and conducted structure-based virtual screening of 1.27 million compounds. Among 100 tested candidates, GI-A14 showed potent, broad-spectrum Antibacterial activity against R. solanacearum, Pseudomonas syringae pv tomato, and Xanthomonas oryzae pv oryzae, with minimum inhibitory concentrations of 1-4 μg/mL. Enzymatic assays confirmed that GI-A14 stabilizes the gyrase-DNA cleavage complex, indicating a DNA-interfacial inhibition mechanism. Furthermore, GI-A14 significantly attenuated the pathogenicity and biofilm formation of R. solanacearum. In planta, GI-A14 provided strong protection against Bacterial wilt, speck, and blight, outperforming the commercial agent zhongshengmycin. These results establish DNA gyrase as a viable molecular target for plant disease control and identify GI-A14 as a promising lead compound for next-generation green bactericides.

Keywords

DNA gyrase; GI-A14; bactericide; molecular target; phytopathogenic bacteria; structure-based virtual screening.

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