海洋链霉菌作为一种重要的药用微生物资源，其基因组中蕴藏着丰富的新型天然产物编码基因簇。然而，大部分基因簇在实验室常规培养条件下处于沉默状态，极大限制了这一药用天然产物资源的开发利用。为了突破这一限制，本项目拟以热带海洋链霉菌新种Streptomyces lohii为研究对象，以前期从其基因组中挖掘到的多条天然产物合成基因簇为出发点，首先对各基因簇编码化合物结构的新颖性进行预测，进而通过基因工程改造技术对潜在编码新结构天然产物的沉默基因簇进行定向激活，最终利用现代天然产物化学分离技术，对该海洋链霉菌中蕴藏的“沉默”天然产物资源进行深度挖掘，并评价其生物活性，为海洋新药开发提供先导分子。本项目旨在通过微生物分子遗传学与天然产物化学的交叉协作，提高新化合物发现的靶向性和效率，探索突破当前海洋链霉菌天然产物研究遇到的瓶颈问题。

Marine streptomycetes are among the most important resources for marine drug discovery. Their genomes contain diverse biosynthetic gene clusters encoding novel natural products. However, a large number of these gene clusters are usually silent under standard cultivation conditions, thus greatly limiting the exploitation of these potential pharmaceutical resources. To address this significant problem, the present project is aimed to uncover the cryptic natural products of a new marine Streptomyces species Streptomyces lohii. Based on the multiple natural product biosynthetic gene clusters identified from S. lohii, targeted activation of the selected cryptical gene clusters, which predictively encode novel compounds, will be performed by genetic manipulations. Finally, with the virtue of modern natural product chemistry, we will deep mine the silent natural product resource of S. lohii to provide new drug leads for the future development of marine drugs. Together, it is anticipated that the opportunity for discovery of new bioactive natural products could be improved. This project attempts to break through the bottleneck problem of marine natural product research by the cooperation of microbial molecular genetics and natural product chemistry.