海洋天然产物近年来受到广泛重视，是发现新药先导化合物最具潜力的领域之一。抗肿瘤是海洋天然产物最典型的活性类型（据NIH统计，从海洋资源中发现抗肿瘤化合物的几率是陆地资源的十倍，而FDA已批准的7个海洋药物中4个为抗肿瘤药物）。统计数据表明，含硫、氮等杂原子的化合物具有更高的成药性。我们在前期研究中从海洋真菌中鉴定了一系列结构新颖的代谢产物，发现若干含硫、含氮化合物对小细胞肺癌、非小细胞肺癌和肝癌等肿瘤细胞具有显著的抑制活性。拟在前期工作的基础上系统开展海洋真菌中含硫、氮等杂原子的代谢产物分子多样性研究，采用优化培养的策略并通过环境胁迫（富营养与寡营养，高盐与低盐、不同的酸碱度等）和添加不同的硫源、氮源等方式激活其沉默代谢途径，诱导产生结构新颖、活性更强、含量更高的含硫、含氮代谢产物，为抗肿瘤药物先导化合物的发现提供科学依据，为海洋天然产物的学科发展提供新的研究策略与思路方法。

Marine natural products (MNPs), which attracted considerable attention in recent years, were regarded as one of the most important resources for the discovery of leading compounds for drug development. The antitumor activity is the most important activity for the MNPs, and, according to the data from NIH, the possibility to discover antitumor compounds from marine resources is ten times more that that from terrestrial resources, while four out of seven FDA-approved marine drugs are used for the cancer treatment. We recently isolated and identified a series of structure unique and biological active compounds from marine-derived fungi, with some sulfur- and nitrogen-containing compounds possess in vitro and in vivo activity against small cell lung cancer, none-small cell lung cancer, and hepatic cancer cells. Based on the above work, this project will focus on the investigation of the diversified sulfur- and nitrogen-containing secondary metabolites from marine-derived fungi, by using of stressed cultural fermentation strategies, such as cultivated on nutrition-rich or limited media, on higher or lower level of salt content of the media with different pH values, to active the silented pathway and to induce the fungi to produce the new secondary metabolites with more potent biologically active in a higher yield. The results from this project is hopefully to provide scientific value for the utilization of fungal metabolites for discovery of leading compounds for antitumor research, and the strategies used in this project will provide new insights/methodologies into the research of marine natural products.