大型食用真菌滑菇次级代谢产物挖掘及生物活性研究

真菌中含有众多结构新颖或活性显著的次级代谢产物，但是能被分离培养的真菌尚不足10%，而且在常规培养条件下，许多真菌次级代谢产物的生物合成基因簇处于沉默状态，导致次级代谢产物的种类远远低于预期。滑菇（Pholiota nameko）是一种大型食用真菌，已实现了菌种的分离培养和人工栽培，但是尚未见其次级代谢产物的报道。前期研究发现，滑菇在不同培养条件下会产生结构各异的次级代谢产物，我们已从其三种不同培养条件的发酵产物中分离鉴定了30多个化合物，包括10多个新化合物。本项目拟采用OSMAC策略（单一菌株产生多种化合物）研究不同培养条件下滑菇次级代谢产物的化学多样性，并结合主成分分析、聚类分析、转录组分析等方法阐明培养条件与次级代谢产物之间的关系，以期从中获得一系列结构新颖或活性显著的次级代谢产物。本项目不仅能充分挖掘滑菇次级代谢产物的合成能力及药用价值，还可为新颖化合物的发现提供一定的方法。

There are many secondary metabolites with novel structure or significant activity in fungi, but less than 10% of them can be isolated and cultured. Moreover, many biosynthetic gene clusters of secondary metabolites in fungi are in silence under the normal culture conditions, resulting in the types of products far lower than expected. Pholiota nameko is a large edible fungus, which has been isolated and cultivated artificially, but its secondary metabolites have not been reported. In the previous study, it was found that different secondary metabolites could be produced in different culture conditions. We have isolated and identified more than 30 compounds from three fermentation products under different culture conditions. In order to obtain secondary metabolites with novel structure or significant activity, OSMAC strategy (one strain many compounds) will be used to study the chemical diversity of secondary metabolites of Pholiota nameko under different culture conditions, and the correlation between culture conditions and secondary metabolites will be clarified by the principal component analysis, cluster analysis, transcriptome analysis and other methods. This project not only can excavate the synthesis ability of the secondary metabolites of Pholiota nameko, but also can provide certain methods for discovering novel compounds.