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.

Efficient Production of Propionic Acid in the Fed-Batch Fermentation of Propionibacterium acidipropionici and Its Metabolic Flux Analysis

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Zhang Y ◽  
◽  
Zhang K ◽  
Li X ◽  
Wang Z ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Batch Fermentation ◽  
Metabolic Flux ◽  
Flux Distribution ◽  
Efficient Production ◽  
Flux Analysis ◽  
Fed Batch ◽  
Propionibacterium Acidipropionici ◽  
Metabolic Flux Distribution ◽  
Fed Batch Fermentation

To improve the fermentation efficiency of Propionibacterium acidipropionici, a simplified metabolic network was established to provide theoretical guidance for medium optimization and process regulation. The effect of glucose and glycerol on propionic acid production and metabolic flux distribution was investigated and the combination of glucose and glycerol was optimized. The results showed that the productivity of propionic acid could be improved by enhancing the synthesis of pyruvate and its flux distribution to the oxaloacetate branch. Finally, the scaled-up fed-batch fermentation of P. acidipropionici was conducted. The concentration of propionic acid reached 51.75 ± 3.62g/L with a glucose/glycerol ratio of 4:1, an improvement of 79.25% relative to the use of glucose alone, and the corresponding productivity and yield were 0.39g/(L· h) and 0.52g/g, respectively. Therefore, the combination of glucose and glycerol significantly improved the productivity of propionic acid and provides a new strategy for industrial production.

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

Measuring non-steady-state metabolic fluxes in starch-converting faecal microbiota in vitro

2010 ◽  
Vol 1 (4) ◽  
pp. 391-405 ◽  
Author(s):  
T. Binsl ◽  
A. De Graaf ◽  
K. Venema ◽  
J. Heringa ◽  
A. Maathuis ◽  
...  
Keyword(s):  
Steady State ◽  
Metabolic Flux ◽  
Flux Distribution ◽  
Computational Modelling ◽  
Total Carbon ◽  
Flux Analysis ◽  
Small Contribution ◽  
Faecal Microbiota ◽  
Isotope Labelling

This paper explores human gut bacterial metabolism of starch using a combined analytical and computational modelling approach for metabolite and flux analysis. Non-steady-state isotopic labelling experiments were performed with human faecal microbiota in a well-established in vitro model of the human colon. After culture stabilisation, [U-13C] starch was added and samples were taken at regular intervals. Metabolite concentrations and 13C isotopomeric distributions were measured amongst other things for acetate, propionate and butyrate by mass spectrometry and NMR. The vast majority of metabolic flux analysis methods based on isotopomer analysis published to date are not applicable to metabolic non-steady-state experiments. We therefore developed a new ordinary differential equation-based representation of a metabolic model of human faecal microbiota to determine eleven metabolic parameters that characterised the metabolic flux distribution in the isotope labelling experiment. The feasibility of the model parameter quantification was demonstrated on noisy in silico data using a downhill simplex optimisation, matching simulated labelling patterns of isotopically labelled metabolites with measured metabolite and isotope labelling data. Using the experimental data, we determined an increasing net label influx from starch during the experiment from 94±1 µmol/l/min to 133±3 µmol/l/min. Only about 12% of the total carbon flux from starch reached propionate. Propionate production mainly proceeded via succinate with a small contribution via acrylate. The remaining flux from starch yielded acetate (35%) and butyrate (53%). Interpretation of 13C NMR multiplet signals further revealed that butyrate, valerate and caproate were mainly synthesised via cross-feeding, using acetate as a co-substrate. This study demonstrates for the first time that the experimental design and the analysis of the results by computational modelling allows the determination of time-resolved effects of nutrition on the flux distribution within human faecal microbiota in metabolic non-steady-state.

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.

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