我们在工业生产菌玫瑰孢链霉菌(Streptomyces roseosporus)SW0702的蛋白酶体缺失株中筛选到降解底物MarR-家族转录调控因子PdrR1，该因子能直接结合达托霉素合成基因簇启动子。本课题将深入研究蛋白酶体降解PdrR1的机制，转录因子PdrR1调控蛋白酶体基因表达、调控自身基因表达、调控达托霉素合成基因簇表达等分子机制，以及达托霉素对PdrR1转录调控作用的反馈调节机制，揭示链霉菌蛋白酶体通过调控转录因子蛋白稳定性进而调节次级代谢过程的分子机制，解析转录因子PdrR1调控达托霉素生物合成的多重正反馈转录调控机制以及次级代谢产物的反馈调控机制，从分子水平解析并建立多层次达托霉素生物合成的调控网络，为工业链霉菌调控途径理性重组进行高产遗传改造提供理论依据。

In the daptomycin industrial producer Streptomyces roseosporus SW0702, we have used proteasome to isolate one of its degradation substrates, a MarR-family transcriptional regulator PdrR1, which could directly bind to the promoter of daptomycin gene cluster. In this project, systemic experiments will be demonstrated to investigate the degradation mechanism of PdrR by the proteasome, and we will also reveal the regulatory mechanism of PdrR1 on the expression of daptomycin gene cluster, proteasomal genes, its own gene pdrR1, and all these regulatory effects on daptomycin production. Furthermore, the feedback effects of daptomycin on PdrR1 transcriptional regulation will also be enthusiastically examined. Thus for the first time we will reveal the regulatory mechanism of proteasome on secondary metabolism by controlling the protein stability of transcriptional regulators, the pleiotropic transcriptional regulatory mechanisms mediated by PdrR1 on daptomycin biosynthesis, and the feedback regulation by secondary metabolites. Thus we will establish the multi-layer molecular regulatory network for daptomycin biosynthesis, and provide the theoretical basis for rational designing and recombinatory genetic engineering of regulatory pathways.