微生物天然产物是发现药物先导化合物的重要源泉。结核病被公认为中国未来20年第一大传染病，非常有意思的是，很多抗结核天然药物都来自于分类学上临近分支菌属的微生物菌株。我们前期从自主构建的我国南海海洋微生物代谢产物库中高通量筛选获得多株海洋疣孢菌新种[1]，其abyssomicin、proximicin类和其它新化合物等都展现出抗结核活性[2]。本研究拟从基因组角度出发，利用基因组挖掘（genome mining）策略，结合多种激活沉默基因簇手段和灵敏的二级质谱小分子网络（NanoDESI-MS/MS networking）检测技术，对实验室海洋疣孢菌菌株次级代谢产物的多样性、生物活性、合成机制、新颖同系物的诱导产生，以及高效表达进行深入的研究，为新型抗结核药物的发现和探索协同进化的奥秘提供理论和物质基础。

Microbial secondary metabolites (MSM) have been an important resource for tuberculosis therapeutics (tuberculosis will be the major infectious disease in next 20 years in China). Intriguingly, many anti-TB MSM are derived from Mycobacterium neighboring genus in taxonomy. Recent advances have been made to accelerate the discovery rate of novel anti-TB drugs including strategies for high-throughput screening from proprietary MSM library, evidenced by isolation of series of new species in Verrucosispora from South China Sea [1]. The resulting compounds, new abyssomicins, proximicins and others, show potent anti-TB activities [2]. In this project, we will focus on bioprospecting of diversity, bio-activities, biosynthesis mechanisms, induction and high efficient production of MSM in dozens of Verrucosispora species by genome mining, activation of cryptic gene clusters and NanoDESI-MS/MS networking techniques. Results gained from the above research will shed lights on discovery of novel anti-TB drug leads and understanding of the evolutionary path of TB.