Aphidicolin为四环二萜类化合物，具有很强的抑制DNA聚合酶α的活性，在上个世纪更是作为抗肿瘤药在欧盟进入临床试验，虽然最后止步于临床1期，但国际上对其研究一直热度不减，目前已获得其衍生物300多个，但尚未发现活性比其更好的衍生物。前期我们从一株深海真菌中获得了77个新aphidicolin衍生物，据此初步建立了其靶向发现方法，并发现了另一aphidicolin生产菌株。基于海洋三所丰富的深海微生物资源，为了快速发现更多的aphidicolin衍生物，本项目拟一方面对目标真菌进行aphidicolin衍生物的靶向分离；另一方面利用离子淌度质谱建立更精确的aphidicolin衍生物靶向发现方法，从MCCC库中寻找更多aphidicolin生产菌株，以期发现更多强活性的aphidicolin衍生物。

Aphidicolin is an active tetracyclic diterpene. It can strongly inhibit the activity of DNA polymerase α. In the last century, it has entered clinical trials as an anti-tumor drug in the European Union. Although it finally stopped in clinical phase 1, it gained extensive research interest internationally. Totally 300 derivatives have been obtained in which only 29 were of natural resources and none of them has better activity than aphidicolin. In our earlier work, our group found 77 new aphidicolin derivatives from a deep-sea fungus. We then established a preliminary targeted discovery method based on high-resolution mass spectrometry and found another producing strain. In order to improve the efficiency and specificity of the finding process of aphidicolin compounds, and to further evaluate the potential of deep sea fungi in producing them, this project plans to carry out the following work. 1) To isolate aphidicolin from the target strain. 2) To study the MS/MS fragmentation behavior of aphidicolin derivatives using UPLC-IMS (Ultra Performance Liquid Chromatography-Ion Mobility Spectrometry), to establish a more accurate targeted discovery strategy for screening them and to construct a screening library. 3) To finish the systematic screening of 1384 crude extracts of 101 deep-sea fungi from the world's largest deep-sea microbial bank MCCC (Marine Culture Collection of China), to find more aphidicolin production strains and to find more potent aphidicolin derivatives.