PDF(Pubmed)
Abstract：
The soil-dwelling filamentous bacteria, Streptomyces, is widely known for its ability to produce numerous bioactive natural products. Despite many efforts toward their overproduction and reconstitution, our limited understanding of the relationship between the host\'s chromosome three dimension (3D) structure and the yield of the natural products escaped notice. Here, we report the 3D chromosome organization and its dynamics of the model strain, Streptomyces coelicolor, during the different growth phases. The chromosome undergoes a dramatic global structural change from primary to secondary metabolism, while some biosynthetic gene clusters (BGCs) form special local structures when highly expressed. Strikingly, transcription levels of endogenous genes are found to be highly correlated to the local chromosomal interaction frequency as defined by the value of the frequently interacting regions (FIREs). Following the criterion, an exogenous single reporter gene and even complex BGC can achieve a higher expression after being integrated into the chosen loci, which may represent a unique strategy to activate or enhance the production of natural products based on the local chromosomal 3D organization.
摘要：
居住在土壤中的丝状细菌，链霉菌,以其生产多种生物活性天然产物的能力而广为人知。尽管为生产过剩和重建做出了许多努力，我们对宿主染色体三维（3D）结构与天然产物产量之间关系的有限理解没有引起注意。这里,我们报告了模型应变的3D染色体组织及其动力学，天黑链霉菌,在不同的生长阶段。染色体经历了从初级代谢到次级代谢的巨大整体结构变化，而一些生物合成基因簇（BGC）在高表达时形成特殊的局部结构。引人注目的是，发现内源性基因的转录水平与由频繁相互作用区域（FIRE）的值定义的局部染色体相互作用频率高度相关。按照标准，外源的单报道基因甚至是复杂的BGC在整合到所选择的基因座后可以获得更高的表达，这可能代表了一种独特的策略来激活或增强基于局部染色体3D组织的天然产物的生产。
