云南省特色中药资源丰富，有悠久的临床应用经验，其中存在着大量的内生菌，由于与宿主的协同进化关系，有些微生物具有了产生与宿主植物相似的药用活性物质的能力。并且在适当的培养条件下能产生结构新颖的活性次生代谢产物，在医药方面具有重要的应用价值。项目拟对从药食同源的三种常用中药三七、当归、石斛中分离得到的4株抗乙酰胆碱酯酶且代谢产物量大的内生菌进行次生代谢产物及其生物活性的研究。从中发现结构新颖、活性较好的化合物，重点进行抗阿尔茨海默病的多靶点乙酰胆碱酯酶抑制剂的发现。项目还拟对其中活性较好的化合物进行诱导微生物代谢途径，富集目标分子，进行构效关系的研究。以从木霉属中发现的特征化合物koninginin为标识分子，探讨其在木霉属真菌的分类学意义。通过本项目的研究预计发现新化合物10-15个，包括1-2个骨架新颖的化合物和1-2个活性较好的化合物，发表2-3篇高水平研究论文，申请1个发明专利。

The resource for chinese traditional medicines were abundant in yunnan province, and many of them have long history in clinical experience. These medicinal plants existed many kinds of endophytes, which have the coevolution with hosts. And some microbes have developed the abilities to produce similar bioactive substances which their host plants produce. Many novel bioactive compounds were found from it in adaptive culture condition, which have important value to the pharmaceutical research. Four endophytic microbes were targeted by anti-acetylcholinesterase and chemical screenings in the strains from Panax notoginseng, Angelica sinensisin, and Dendrobium candidum, three common traditional Chinese medicine in yunnan province. The research of bioactive secondary metabolites from this 4 endophytes will be carried out to find novel active compounds.The multi-target active compounds against acetylcholinesterase for Alzheimer’s disease therapy were studied. More strong active compounds will be otained by inducing biotransformation of active ingredient in microorganism for the research of structure-activity relationship. Koninginins, the characteristic compounds from Trichoderma were used as marker in microbial taxonomy. 10-15 new compounds including of 1-2 unprecedented skeleton compounds and 1-2 bioactive constituents will be found through this project. 2-3 SCI papers will be published, and 1 patent will be applied for.