Construction And Analysis Of In Tegrated Cellular Network Of Corynebacterium Glutamicum

Corynebacterium glutamicum is an important traditional industrial microorganisms, and has been widely used in industrial production of amino acids, vitamins and nucleotides. With the rapid development of genomics and molecular genetic manipulation tools, it has been receiving more and more attentions towards a novel versatile cellular factory. However, relative to E. coli and other model organisms, there is few studies in the metabolic regulation of the Corynebacterium, particularly lack of studys of the integrated cellular networks of Corynebacterium glutamicum, the mechanism of high yield and metabolic regulation not yet clear, which severely retards the systematic study and large-scale rational design and optimization of the Corynebacterium glutamicum strains.In this study, we constructed an integrated cellular network of Corynebacterium glutamicum for the first time and built the gene transcriptional regulatory and metabolic local database by combined use of KEGG, CoryneRegnet and literature resources. The integrated network contained1384reactions,1276compounds,88regulators,999pairs of transcriptional regulation relationships. We found8transcriptional and metabolic level synergy regulation relationships in it, which could not be achieved in a single network.Meanwhile, we analysed Corynebacterium glutamicum cellular network topological structure and function based on the network analysis tools such as Pajek and Cytoscape. The results indicated that the transcriptional regulation relationship including five major function modules and8global regulators could be divided into five layers. In addition, the metabolic network showed a clear bow-tie structure, which contributed to improve the robustness and save resource for microorganisms.In addition, we also proposed a new method to extract metabolic and regulatory sub-network from integrated cellular network taking lysine biosynthesis as an example. Compared with the traditional lysine biosynthetic pathway, this sub-network did not only include more metabolic pathways but also corresponding enzyme and its regulatory information, which would be greatly helpful for understanding the hyper-production mechanisms for amino acids and the re-design of the industrial strains, and laid a foundation for further integrated cellular network dynamic prediction of simulation and cell factory rational design.