香椿内生炭角菌新颖抗菌先导结构的发现及活性筛选

The resistance of plant pathogens to fungicides is one of the most prominent problems in agricultural production and pesticide industry. Screening of new pesticide lead compounds from natural products has become one of the effective ways to solve this problem. Plant endophytic fungi as a special environment microbial has increasingly draw much attention of the researchers because of its complex metabolic pathways and diverse metabolic species. The project intended to study the endogenous Xylaria sp. associated with medicinal plant Toona sinensis. The following researches were carried out: 1) based on the deduplication analysis method of HPLC-QTOF-MS/MS and microbial product induction technology, to quickly identify novel chemical structures from Xylaria sp. 2) based on the chemical epigenetic modification strategy, to establish the controllable technical measures to activate the "silence" secondary metabolic pathway in Xylaria sp. to ensure the production of new products. 3) to evaluate the anti-phytopathogenic fungal activity of the new compounds, and to discover antimicrobial lead compounds with potential application value. Through the study of this project, it is expected to discover new pesticide lead compounds with significant anti-phytopathogenic fungi activity, and to provide new ideas and methods for the discovery of novel architectures and more active biogenic fungicides.

植物病原菌对杀菌剂的抗药性是目前农业生产和农药工业所面临的最突出的问题，从天然产物中筛选新型农药先导化合物已成为解决这一问题的有效途径之一。植物内生菌作为一种特境微生物，因其代谢途径复杂，代谢产物种类多样而日益受到研究者的重视。本项目拟以一株分离自药用植物香椿的内生炭角菌（Xylaria sp.）为研究对象，开展以下研究：1）基于HPLC-QTOF-MS/MS的去重复分析方法和微生物产物诱导技术，快速发现并鉴定炭角菌中骨架新颖的化学结构。2）基于化学表观遗传修饰策略，建立可调控的技术措施，激活炭角菌中“沉默”次生代谢途径，确保系列新产物的产生。3）评价新化合物的抗植物病原真菌活性，发现具有潜在应用价值的抗菌先导化合物。通过本项目的研究，有望发现具有显著抗植物病原菌活性的新农药先导化合物，为寻找结构更新、活性更强的生物源杀菌剂提供新的思路和方法。

植物内生菌是功能天然产物的重要来源之一，本项目以香椿内生真菌为研究材料，开展了系列的研究工作，探究其丰富独特的次级代谢产物，发现新化合物，深入挖掘具有杀虫、除草、抗炎和抗真菌等活性的天然产物，发现有成药前景的新药先导化合物，为新药开发提供理论研究基础。主要取得的研究进展及成果如下：.①建立了2套可激活炭角菌中“沉默”次生代谢途径的方法，并成功诱导该菌产生了一系列新化合物。.②分离并鉴定61个化合物，其中22个为新化合物。.③筛选出5个具有抗植物病原真菌活性的新农药先导化合物，另外包括4个具有除草活性，2个具有抗炎活性，1个具有抗临床耐药菌的化合物。.④发表 SCI 论文 4篇，申请专利1件，培养研究生 3 名。