药用植物蕲艾内生真菌代谢产物分子多样性与抗海洋病害菌活性研究

中国是水产养殖大国，随着养殖规模的扩大和集约化程度的提高，病害的发生频率和影响程度越来越大，迫切需要研发新的抗海洋病害菌活性物质。从亲缘关系较远的物种中更有可能发现作用显著的活性分子。蕲艾是湖北蕲春著名道地药材，我们前期研究发现其富含内生真菌，经筛选发现两种木霉属内生真菌QA-3和QA-8的代谢产物丰富且具有显著的抗海洋病害菌活性，进一步研究发现在不同培养条件下QA-3和QA-8能产生不同类型的代谢产物,已从中发现活性显著的含缩酮结构特征的聚酮和结构新颖的二萜类化合物。拟在此基础上采取环境胁迫等手段深入挖掘上述内生真菌代谢产物的分子多样性，构建蕲艾-内生真菌-（人工诱导）抗菌活性相结合的研究模式，建立蕲艾内生真菌代谢产物高效灵敏的分离检测体系，发现结构新颖、活性显著的代谢产物，探讨蕲艾内生真菌次生代谢的分子多样性与活性并总结、获得构效关系规律，为我国药用植物内生真菌资源的利用提供科学依据。

Aquaculture is a mega-industry in China. With the expansion of the scale and intensive degree of aquaculture, the incidence of diseases and the degree of impacts are increasing very quickly, and there is urgent need to discover new bioactive substances to against the marine pathogens. It is likely easier to find active substances for anti-marine pathogens from the species that genetically far from marine organisms. Qiai (Artemisia argyi), growing in Qichun County of Hubei Province, is a famous Chinese herbs with long history for the treatment of various diseases. In the preliminary screening we found that this mugwort is rich in endophytic fungi, with two species (QA-3 and QA-8) belonging to the genus Trichoderma have prolific metabolites and strong activity against marine pathogens, and some polyketides having ketal substructures with potent activity against auqticpathogens and some diterpenoids with rare skeleton have been identified from the fungal strain QA-3. Further works revealed that these two strains (QA-3 and QA-8) could produce various metabolites in different culturing conditions. Based on these work, the current project will focus on mining the molecular diversity of the secondary metabolites of these two strains by using of a kind of cultivation on environment-stressed culture conditions. By constructing a research mode with combination of Qiai-endophyte and stress-induced biological activity, and by employing modern chromatographic and spectral methods, a sensitive and efficient separation/purification and identification system to obtain various metabolites with new structure and strong activity will be approached. The molecular diversity of the metabolites and structure–activity relationships will be disclosed. The project will provide scientific basis for the sustainable utilization of endophytic resources in Chinese medicinal plants.