摘要
以克雷伯氏杆菌基因组尺度代谢网络模型iYL1228为研究对象,应用基于热力学约束的通量可变性分析对代谢路径进行冗余性分析。首先对iYL1228添加热力学约束应用通量平衡分析,确定底物甘油单位生产率达到最大时的最优路径以及依赖还原当量NADH的可调控反应;然后应用添加热力学约束的通量可变性分析研究了最优路径中依赖NADH的可调控反应对路径冗余性的影响。结果表明:在最优路径中,依赖还原当量的可替代反应乙醛脱氢酶ACALD、谷氨酸脱氢酶GLUDx和转氢酶NADTRHD对路径冗余性影响较大,其反应通量越大,路径冗余性越差;而依赖还原当量的必需反应甘油脱氢酶GLYCDx和苹果酸脱氢酶MDH对路径冗余性影响较小,可用于后期的辅因子特异性优化分析。
In this paper,the genome-scale metabolic network model iYL1228 of Klebsiella pneumoniae was used to analysis the metabolic pathway redundancy by using the flux variability analysis based on thermodynamic constraint.The flux balance analysis based on thermodynamic constraint was applied to determine the optimal pathway when the substrate specific productivity of glycerol was maximum and the regulatable NADH-dependent reactions.Then the effects of these regulatable reactions on pathway redundancy were studied with flux variability analysis based on thermodynamic constraint.Results showed that the substituable NADH-dependent acetaldehyde dehydrogenase,glutamate dehydrogenase and NAD transhydrogenase reactions in the optimal pathway had a great influence on the pathway redundancy and the pathway redundancy decreased as its flux increased.However,the essential NADH-dependent glycerol dehydrogenase and malate dehydrogenase reactions had littleeffect on the pathway redundancy,which could be used in the later optimization of the cofactor specificity.
出处
《青岛科技大学学报（自然科学版）》
CAS
2017年第6期18-23,共6页
Journal of Qingdao University of Science and Technology:Natural Science Edition
基金
山东省自然科学基金项目(ZR2013BM001)
关键词
克雷伯氏杆菌
路径冗余性分析
热力学约束
还原当量
通量可变性分析
Klebsiella pneumoniae
pathway redundancy analysis
thermodynamic constraint
reducing equivalent
flux variability analysis
