谷氨酸棒状杆菌集成细胞网络的构建与结构分析

Construction and structural analysis of integrated cellular network of Corynebacterium glutamicum

谷氨酸棒状杆菌是一种重要的传统工业微生物,其基因组学和分子遗传操作工具的快速发展使得谷氨酸棒状杆菌具备了作为新型细胞工厂的潜力。但是,相对于大肠杆菌等模式生物,对于棒杆菌的代谢调控研究较少,特别是目前还缺乏谷氨酸棒状杆菌集成细胞网络的研究,这一现状阻碍了谷氨酸棒状杆菌的系统生物学研究和大规模菌种理性设计优化。文中综合应用公共数据库、文献数据库资源,首次构建了谷氨酸棒状杆菌的集成细胞网络,包含1 384个反应,1 276个代谢物,88个调节子,999对转录调控关系。其转录调控可分为5层,代谢网络呈现出清晰的bow-tie结构。文中还以赖氨酸的生物合成为例,提出了一种提取代谢调控子网络的新方法,这对氨基酸等产品高产生物机制的研究和工程菌株的重新设计具有指导意义。

Corynebacterium glutamicum is one of the most important traditional industrial microorganisms and receiving more and more attention towards a novel cellular factory due to the recently rapid development in genomics and genetic operation toolboxes for Corynebacterium.However,compared to other model organisms such as Escherichia coli,there were few studies on its metabolic regulation,especially a genome-scale integrated cellular network model currently missing for Corynebacterium,which hindered the systematic study of Corynebacterium glutamicum and large-scale rational design and optimization for strains.Here,by gathering relevant information from a number of public databases,we successfully constructed an integrated cellular network,which was composed of 1 384 reactions,1 276 metabolites,88 transcriptional factors and 999 pairs of transcriptional regulatory relationships.The transcriptional regulatory sub-network could be arranged into five layers and the metabolic sub-network presented a clear bow-tie structure.We proposed a new method to extract complex metabolic and regulatory sub-network for product-orientated study taking lysine biosynthesis as an example.The metabolic and regulatory sub-network extracted by our method was more close to the real functional network than the simplex biochemical pathways.The results would be greatly helpful for understanding the high-yielding biomechanism for amino acids and the re-design of the industrial strains.