The Pathway Opti Mization Analysis Of 1, 3-Propanediol Production With Klebsiella Pneumoniae Based On Genome Scale Network

Metabolic engineering can manipulate the metabolic pathway of microorganism to meet the specific needs of human, and clarify the relationship between metabolic pathways and metabolic network, then achieving the purpose of optimizing cell performance. It has been widely used in the fermentation industry and has made a significant contribution to the industrial microorganism. At present, the yield of 1,3-propanediol using biochemical method is not very high, in this paper, we studied metabolic network flexibility, the optimal pathway of 1,3-propanediol and its redundancy of alternative pathway with K. pneumoniae based on genome scale network in order to improve its yield.Firstly, we carried out geometric flux balance analysis with maximation of specific rate of 1,3-propanediol, it provided a optimal metabolic pathway and the maximum theoretical yield of 0.874. Then we further studied the effects of different specific growth rates on the optimal pathway of 1,3-propanediol and found the critical point which the optimal pathway changing. It was seen that the reaction number of optimal metabolic pathway of 1,3-propanediol was changed, more 35 reactions appeared and 9 reactions disappeared as the specific growth rate increasing. The transportation of intracellular sodium ion and reduction equivalent have important influence on the biomass synthesis. The values of reduction equivalent NADH used for synthesis of biomass and glutamatethe, maintaining the balance of intracellular sodium ion concentration were increased, so it led to the decrease of NADH used for the synthesis of 1,3-propanediol.Secondly, we analyzed the redundancy of 1,3-propanediol metabolic pathway using flux variability analysis. We analyzed the effect of specific growth rate,specific rate of 1,3-propanediol, and reaction flux of GLYK, GLYCDx on the redundancy of metabolic pathway. We obtained that all reaction flux in the 1,3-propanediol pathway was adjusted to a lower value can obtain a high redundancy and high yield. When the specific rate of 1,3-propanediol was about 64 percent of its maximum theoretical value, the maximum yield can be obtained.Metabolic flexibility of microorganism cells varies with changing environment and plays an important role in the yield of target production. Finally, we used flux variability analysis to find the influence of specific growth rate, the internal reactions and exchange reactions on the metabolic flexibility, it was seen that the change of specific growth rate was the only major factors affecting the metabolic flexibility and controlling growth rate to suboptimal can make its greater metabolic flexibility. We further studied how the metabolic flexibility depended on the change of growth rate and summed up the two necessary conditions for improving metabolic flexibility, boosting the microorganisms ability to deal with the external environment change.