基因组尺度克雷伯氏杆菌代谢甘油产1,3-丙二醇的路径分析

Pathway Analysis of 1,3-Propanediol Production with Glycerol Based on Genome Scale Network of KlebsiellaPneumoniae

采用代谢网络分析软件COBRA Toolbox对克雷伯氏杆菌基因组尺度的网络以1,3-丙二醇产量最大为目标函数进行通量平衡几何分析,得出不同细胞生长速率下克雷伯氏杆菌代谢甘油产1,3-丙二醇的最优路径及反应通量值的分布,找出细胞生长速率影响1,3-丙二醇产量的根本原因。结果显示:1,3-丙二醇最优代谢路径的反应个数随细胞生长速率的不同而不同,随着细胞生长速率的增加,共有34个反应加入到最优代谢路径中,9个反应从最优路径中消失;胞内钠离子的运输及还原当量NADPH(还原型辅酶Ⅱ)、NADH(还原型辅酶Ⅰ)对细胞生长速率的合成有重要影响,随着细胞生长速率的增加,还原当量NADPH、NADH所需值也增加,同时,用于维持胞内钠离子浓度的平衡和谷氨酸的合成的NADH消耗量也增加,导致用于合成1,3-丙二醇的还原当量值减少。

In recent years, the improvment of 1,3-propanediol production using metabolic engineering is a research hotpot. This article used the metabolic network analysis soft- ware COBRA Toolbox carrying out flux balance geometry analysis with genome scale of Klebsiella pneumoniae network by 1,3-propanediol production as the objective function. The different optimal metabolic pathways of glycerol and flux distribution of each reaction with Klebsiella pneumoniae under different values of biomass were obtained and the influence of biomass on the production of 1,3-propanediol were analyzed. It was seen that the reaction number of optimal metabolic pathway of 1,3-propanediol was changed, more 34 reactions appeared and 9 reactions disappeared from the optimal pathway as the biomass growth rate. The transportation of intracellular sodium ion and reduction equivalent have important influence on the biomass synthesis. The values of reduction equivalent NADPH and NADH used for biomass synthesis and the reduction equivalent NADH used for maintaining the balance of intracellular sodium ion concentration and the synthesis of glutamate were increased with biomass increasing, so it led to the decrease of NADH used for the 1,3-propanediol synthesis.