scholarly journals Agent Clustering Strategy Based on Metabolic Flux Distribution and Transcriptome Expression for Novel Drug Development

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1640
Author(s):  
Yao Ruan ◽  
Xiao-Hui Chen ◽  
Feng Jiang ◽  
Yan-Guang Liu ◽  
Xiao-Long Liang ◽  
...  
Keyword(s):  
Metabolic Flux ◽  
Flux Distribution ◽  
Drug Repositioning ◽  
Enrichment Analysis ◽  
Network Module ◽  
Metabolic Flux Distribution ◽  
Traditional Drug ◽  
Metabolic Reactions ◽  
Transcriptome Expression ◽  
Novel Drug

The network module-based method has been used for drug repositioning. The traditional drug repositioning method only uses the gene characteristics of the drug but ignores the drug-triggered metabolic changes. The metabolic network systematically characterizes the connection between genes, proteins, and metabolic reactions. The differential metabolic flux distribution, as drug metabolism characteristics, was employed to cluster the agents with similar MoAs (mechanism of action). In this study, agents with the same pharmacology were clustered into one group, and a total of 1309 agents from the CMap database were clustered into 98 groups based on differential metabolic flux distribution. Transcription factor (TF) enrichment analysis revealed the agents in the same group (such as group 7 and group 26) were confirmed to have similar MoAs. Through this agent clustering strategy, the candidate drugs which can inhibit (Japanese encephalitis virus) JEV infection were identified. This study provides new insights into drug repositioning and their MoAs.

scholarly journals Barth syndrome cells display widespread remodeling of mitochondrial complexes without affecting metabolic flux distribution

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 ◽  
...  
Keyword(s):  
Metabolic Flux ◽  
Flux Distribution ◽  
Barth Syndrome ◽  
Metabolic Flux Distribution ◽  
Mitochondrial Complexes

Impacts of Sodium Citrate on Metabolic Flux Distributions of L-Valine Fermentation

2011 ◽  
Vol 343-344 ◽  
pp. 643-648
Author(s):  
Qing Yang Xu ◽  
Lei Ma ◽  
Xi Xian Xie ◽  
Ning Chen ◽  
Jian Wang
Keyword(s):  
Corynebacterium Glutamicum ◽  
Culture Medium ◽  
Metabolic Flux ◽  
Sodium Citrate ◽  
Flux Distribution ◽  
Metabolic Flux Distribution ◽  
Key Nodes

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.

Metabolic flux analysis of simultaneous production of vitamin B12 and propionic acid in a coupled fermentation process by Propionibacterium freudenreichii

2021 ◽  
Author(s):  
Yuhan Zhang ◽  
Xiaolian Li ◽  
Ziqiang Wang ◽  
Yunshan Wang ◽  
Yuanyuan Ma ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Fermentation Process ◽  
Metabolic Flux ◽  
Flux Distribution ◽  
Vitamin B ◽  
Flux Analysis ◽  
Propionibacterium Freudenreichii ◽  
Simultaneous Production ◽  
Metabolic Flux Distribution ◽  
New Strategy

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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