Identification of propranolol and derivatives that are chemical inhibitors of phosphatidate phosphatase as potential broad-spectrum fungicides  

作　　者：Juan Zhao Yu Chen Zhifen Ding Yaru Zhou Ruiqing Bi Ziting Qin Lei Yang Peng Sun Qiping Sun Guang Chen Daiyuan Sun Xianya Jiang Lu Zheng Xiao-Lin Chen Hu Wan Guanghui Wang Qiang Li Huailong Teng Guotian Li 

机构地区：[1]National Key Laboratory of Agricultural Microbiology,Hubei Hongshan Laboratory,Hubei Key Laboratory of Plant Pathology,The Center of Crop Nanobiotechnology,Huazhong Agricultural University,Wuhan 430070,China [2]College of Science,Huazhong Agricultural University,Wuhan 430070,China [3]National Key Laboratory of Crop Genetic Improvement,Huazhong Agricultural University,Wuhan 430070,China [4]State Key Laboratory of Crop Stress Biology for Arid Areas,College of Plant Protection,Northwest A&F University,Yangling 712100,China [5]College of Chemistry and Life Sciences,Sichuan Provincial Key Laboratory for Development and Utilization of Characteristic Horticultural Biological Resources,Chengdu Normal University,Chengdu 611130,China [6]Yangjiang Institute of Agricultural Sciences,Yangjiang 529500,China

出　　处：《Plant Communications》2024年第1期215-230,共16页植物通讯（英文）

基　　金：supported by the National Key R&D Program of China (2022YFA1304402);the National Natural Science Foundation of China (31801723,32172373);the Fundamental Research Funds for the Central Universities to G.L. (2023ZKPY002,2662023PY006,AML2023A);Q.L.(2662020ZKPY005).

摘　　要：Plant diseases cause enormous economic losses in agriculture and threaten global food security,and application of agrochemicals is an important method of crop disease control.Exploration of disease-resis-tance mechanisms and synthesis of highly bioactive agrochemicals are thus important research objectives.Here,we show that propranolol,a phosphatidate phosphatase(Pah)inhibitor,effectively suppresses fungal growth,sporulation,sexual reproduction,and infection of diverse plants.The MoPah1 enzyme activity of the rice blast fungus Magnaporthe oryzae is inhibited by propranolol.Alterations in lipid metabolism are associated with inhibited hyphal growth and appressorium formation caused by propranolol in M.oryzae.Propranolol inhibits a broad spectrum of 12 plant pathogens,effectively inhibiting infection of barley,wheat,maize,tomato,and pear.To improve antifungal capacity,we synthesized a series of propranolol derivatives,one of which shows a 16-fold increase in antifungal ability and binds directly to MoPah1.Propranolol and its derivatives can also reduce the severity of rice blast and Fusarium head blight of wheat in thefield.Taken together,our results demonstrate that propranolol suppresses fungal development and infection through mechanisms involved in lipid metabolism.Propranolol and its derivatives may therefore be promising candidates for fungicide development.

关 键 词：PROPRANOLOL molecular design chemical modification VIRULENCE lipid metabolism Pyricularia oryzae 

分 类 号：Q94[生物学—植物学]