课题选择可产生活性次生代谢产物，代谢产物具有一定结构特点，并完成全基因组测序的几株深海微生物为研究对象，开展以核受体为靶点的先导化合物发现、形成规律及作用机制的研究。本课题以深海细菌B5为主要研究对象，以24碳大环内酯类化合物为参照物，以二维制备色谱有序分离为手段，针对B5沉默基因激活和等离子突变文库，从基因水平上开展新化合物的发现、生物合成途径阐述、核受体靶点生物学机制研究和合成生物学元件探索等工作，力求在发展天然药物化学研究方法、探索天然产物形成规律方面取得一些进展，为先导化合物的发现与研究奠定基础。

In this project, isolation, structural elucidation and molecular mechanism involved in RXR and Nur77 pathway of secondary metabolites from deep-sea Bacillus subtilis B5 and its mutation libraries and some deep sea derived fungi are carried out. By taking the advantages of two-dimensional chromatographic separation techniques, this proposal aims to establish the biological target research platforms for marine drugs or secondary metabolites from deep-sea microorganisms. In order to understand the target molecular mechanism of bioactive molecules and develop new research strategy for natural drug targets, Macrolactins and other secondary metabolites from B5 bacteria via sequencing and mutation analysis will be inverstigated by new approaches for activating silent biogenetic gene clusters in marine microorganisms. It will also help to develop new methods to evaluate the molecular mechanism of marine drugs and build the theoretical basis of lead compound discovery and exploiation, by using modern molecular pharmacology.