从微生物出发寻找新活性天然产物一直是药物和生物农药开发先导性化合物的重要来源。然而传统研究方法的随机性和盲目性，使得大量已知化合物被重复性的发现。如何导向性地从微生物中发现特定活性新天然产物是摆在天然产物化学研究者面前的一道难题。我们前期工作首次运用高通量筛选和基因组导向分析的策略，从烟草来源内生真菌中发现了一类结构新颖的显著抗烟草花叶病毒活性吲哚生物碱。初步结果表明：高通量筛选结合基因组导向分离策略有可解决导向发现新功能天然产物的难题。为了验证这一设想，我们将针对前期抗烟草花叶病毒活性高通量筛选得到的内生菌来源活性分子宿主进行基因组测序和活性分子生物合成基因簇分析，利用现有基因簇作为模板寻找到可能含有类似基因簇的菌株，利用基因组导向分离挖掘候选菌株中目标活性成分。本课题将首次利用高通量筛选和基因组导向分析的新视点，为更加高效的发现抗烟草花叶病毒活性新天然产物提供一定的思路。

Finding novel natural products from the microbic source is always one of the best way to generate lead compounds. However, large scales of know natural products were repeated discovered by random method. It is very difficult for almost all of the natural product researcher to guided find target bioactive natural products from microorganism. The pre-experimental results showed that a series of novel anti-TMV indole alkaloids were found by high throughput screening (HTS) coupled with genome mining method from endophytic fungi isolated from Nicotiana tabacum. Therefore, we hypothesized that HTS coupled with genome mining strategies might be used to guide discovering of bioactive natural product. In order to verify this hypothesis, we will firstly genome sequence of the strains selected by HTS based on the anti-TMV activity and then to isolate the bioactive compounds and elucidating the compound’s biosynthetic gene cluster. Secondly, we will use the candidate gene cluster to do a blast and find it’s homologous gene clusters and their strains. Lastly, we will active these homologous gene clusters and guiding isolate and identify the bioactive natural products from these strains. This project will firstly use HTS coupled with genome mining strategies to finding navel anti-TMV natural products from natural source. In addition, we also hope that this project could provide new ideas for guiding discovering novel anti-TMV natural product from natural source.