ITS-HPLC-HRMS-Bioassay多级筛选策略指导下海洋真菌中新型抗菌活性产物的发现

The investigation of structurally novel and biologically active compounds from marine-derived fungi has become a noticeable research area in natural drug discovery, as an important source for new drug leads. Recently, facing with increasing troubles of strain of "replication of research" and the active compound "duplicate discovery", in order to search for novel bioactive natural products quickly, our group initiated a program of rapid screening for new compounds based on ITS-HPLC-HRMS-Bioassay integrated methods. Here, we will conduct the following research using sponge-associated fungi as materials: 1) to gain the targeted strain based on inhibitory activity against Vibrio parahaemolyticus and species identification. 2) to rapidly separate and elucidate the active compounds from strain according to their activity screening and database search results, followed by HPLC-PDA-HRMS analysis for the UV and HRMS information of the metablite fractions. The approaches used in this study will greatly accelerate the discovery of some new anti-bacteria fungal secondary metabolite, and will provide a scientific basis for the effective use of marine fungi.

海洋真菌次级代谢产物已成为天然产物研究的热点领域，是寻找新型药物先导化合物的重要资源。面对近来研究中越来越多的出现菌株“重复研究”和.活性化合物“重复发现”问题，为了高效的快速发现并分离真菌中有研究价值的活性化合物，本课题以海洋来源真菌为研究对象，基于建立的ITS-HPLC-HRMS-Bioassay相结合的活性产物快速检识方法，开展如下研究：1)以副溶血弧菌抑制活性和种属鉴定结果为指导确定目标菌株。2)运用HPLC-PDA-HRMS分析发酵产物各馏分色谱峰的UV和HRMS信息，根据其活性及数据库检索结果为指导，对活性化合物进行快速的追踪分离和结构解析。该研究会发现一批具有新颖结构且抗菌活性显著的真菌代谢产物，为真菌资源的有效利用提供一定的科学依据。

海洋真菌次级代谢产物是寻找新型药物先导化合物的重要资源。但是近年来出现菌株重复研究和化合物重复发现等问题制约天然产物研究发展，为了更加快速有效地发现并分离真菌中有研究价值的活性化合物，本项目利用ITS-HPLC-PDA-HRMS-Bioassay组合筛选策略对海洋活性真菌进行研究，在OSMAC策略指导下，运用分子网络-活性集成筛选方法，本项目完成了4株海洋来源真菌Paraphaeosphaeria sp. PJX5、Talaromyces amestolkiae PJX71、Sporendonema casei HDN16-802和Chaetomium globosum HDN151398的活性次级代谢产物研究，共获得27个化合物，其中新化合物10个，包括2个α-吡喃酮类、5个蒽酮衍生物和3个偶氮苯基生物碱, 获得了具有抗菌、细胞毒等较强生物活性的新化合物6个，其中5个具有较强抗菌活性，1个具有较好的抗肿瘤活性。上述研究在Journal of Natural Products、Marine Drugs杂志发表SCI收录论文3篇，申请专利2项，其中获授权专利1项。该研究为提高海洋真菌新活性化合物的发现效率做出了有益的探索，为进一步推动先导抑菌化合物的研究及真菌资源的有效利用奠定了基础。