靶标酶在新农药研发中具有极其重要的作用，大多数高活性农用杀菌剂的作用靶标都是病原物的各种代谢酶系统。FabH是控制细菌脂肪酸生物合成的关键酶，以其为靶标有望开发出对细菌具有选择性而对高等生物无危害的高效、低毒、专一性好的新型杀菌剂。在前期工作基础上，本项目首先通过对杀菌剂靶标酶FabH的固定化研究，制成亲和色谱柱，并与LC-UV-MS系统联用，建立一套快速识别复杂组分中杀菌活性成分的检测与分析体系；其次，以代谢产物结构丰富的植物内生菌为资源，运用该体系从其发酵产物中识别具有FabH抑制活性的组分，进行定点分离和结构鉴定；最后，通过全面的生物活性评价及模拟分子对接，研究化合物杀菌活性、与靶标作用方式及其对作物的安全性，以发现结构新颖、活性显著、选择性好适宜进一步开发的新型杀菌剂先导化合物。本项目将为农药先导化合物的快速发现提供一套具有广泛适用性的高效筛选模式，以促进我国新农药创制研究的发展。

The target enzymes play an important role in the research and development of new pesticides. Most of the targets of highly active fungicides or bactericides are the key enzymes in the metabolism of pathogens. FabH is such a key enzyme that controls the bacterial fatty acid biosynthesis. Inhibitors against FabH are expected to be developed as novel bactericide with high efficiency, low toxicity and good specificity. Based on our preliminary studies, this project aims to investigate the novel secondary metabolites as antagonists in the plant disease control by utilizing endophytes and FabH as resource and identification tool, respectively. Firstly, FabH will be immobilized on composite carrier to prepare affinity chromatography column with specific enzyme bioactivity through immobilization reaction. Coupled with the LC-UV-MS instrument, a system used for efficient and rapid detection and anaylsis of antibacterial active constituents will be established. Then rapid screening for compounds with FabH inhibitory activity from the endophytic fungi will be conducted using this system. Following the tracking separation, structure identification, simulative molecular docking and intensive bioactivity validation, lead compounds with novel structure, significant activity and good selectivity will be finally discovered. It will also provide an effitive and widely applicable screening model for pasticide lead compounds discovery, and promote the development of China’s new pesticide innovation.