Impact Analysis of Gene Deletion on the Metabolic Flux Distribution of E.coli and on Its Flux-Backbone: Genome-Scale Simulation Approach

Author(s):  
Zixiang Xu ◽  
Xie Jianming ◽  
Xinan Yang ◽  
Sun Xiao
2021 ◽  
Author(s):  
Sudharshan Ravi ◽  
Rudiyanto Gunawan

AbstractGenome-scale metabolic models (GEMs) provide a powerful framework for simulating the entire set of biochemical reactions occurring in a cell. Constraint-based modeling tools like flux balance analysis (FBA) developed for the purposes of predicting metabolic flux distribution using GEMs face considerable difficulties in estimating metabolic flux alterations between experimental conditions. Particularly, the most appropriate metabolic objective for FBA is not always obvious, likely context-specific, and not necessarily the same between conditions. Here, we propose a new method, called ΔFBA (deltaFBA), that employs constraint-based modeling, in combination with differential gene expression data, to evaluate changes in the intracellular flux distribution between two conditions. Notably, ΔFBA does not require specifying the cellular objective to produce the flux change predictions. We showcased the performance of ΔFBA through several case studies involving the prediction of metabolic alterations caused by genetic and environmental perturbations in Escherichia coli and caused by Type-2 diabetes in human muscle.


2018 ◽  
Vol 1864 (11) ◽  
pp. 3650-3658 ◽  
Author(s):  
Iliana A. Chatzispyrou ◽  
Sergio Guerrero-Castillo ◽  
Ntsiki M. Held ◽  
Jos P.N. Ruiter ◽  
Simone W. Denis ◽  
...  

2011 ◽  
Vol 343-344 ◽  
pp. 643-648
Author(s):  
Qing Yang Xu ◽  
Lei Ma ◽  
Xi Xian Xie ◽  
Ning Chen ◽  
Jian Wang

The effect of sodium citrate on the metabolic flux distributions in the middle and late periods of L-valine production by Corynebacterium glutamicum XV0505 was obtained. It was shown that when sodium citrate (2.0 g/L) was added into the initial fermentation culture medium, the metabolic flux of Embden-Meyerhof-Parnas (EMP) route decreased from 96.43 to 91.13, and the metabolic flux of Hexose Monophophate (HMP) route increased from 3.56 to 8.87, and the metabolic flux flowing to L-alanine and acetate was decreased by 21.1% and 32.4%, respectively. Meanwhile, the metabolic flux of biosynthesis route of L-valine was increased by 10.74%. Therefore, sodium citrate can change the metabolic flux distribution in the key nodes of biosynthesis route of L-valine, decrease the generation of byproducts, and increase the metabolic flux in the biosynthesis route of L-valine.


2021 ◽  
Author(s):  
Yuhan Zhang ◽  
Xiaolian Li ◽  
Ziqiang Wang ◽  
Yunshan Wang ◽  
Yuanyuan Ma ◽  
...  

Abstract The metabolic processes involved in simultaneous production of vitamin B12 and propionic acid by Propionibacterium freudenreichii are very complicated. To further investigate the regulatory mechanisms of this metabolism, a simplified metabolic network was established. The effects of glucose feeding, propionic acid removal, and 5,6-dimethylbenzimidazole (DMB) addition on the metabolic flux distribution were investigated. The results showed that synthesis of propionic acid can be increased by increasing the metabolic flux through the oxaloacetate and methylmalonyl-CoA branches in the early and middle stages of the coupled fermentation. After DMB addition, the synthesis of vitamin B12 was significantly enhanced via increased metabolic flux through the δ-aminolevulinate branch, which promoted the synthesis of uroporphyrinogen III, a precursor of vitamin B12. Therefore, the analysis of metabolic flux at key nodes can provide theoretical guidance for the optimization of P. freudenreichii fermentation processes. In an experimental coupled fermentation process, the concentrations of vitamin B12 and propionic acid reached 21.6 and 50.12 g/L respectively, increased by 105.71% and 73.91% compared with batch fermentation, which provides a new strategy for industrial production.


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