scholarly journals Identifying and Engineering Bottlenecks of Autotrophic Isobutanol Formation in Recombinant C. ljungdahlii by Systemic Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Maria Hermann ◽  
Attila Teleki ◽  
Sandra Weitz ◽  
Alexander Niess ◽  
Andreas Freund ◽  
...  
Keyword(s):  
Metabolic Profiling ◽  
Ehrlich Pathway ◽  
Current Generation ◽  
Physiological Characterization ◽  
Flux Balance ◽  
Clostridium Ljungdahlii ◽  
Systemic Analysis ◽  
Balance Analysis ◽  
Different Strains ◽  
Stirred Bioreactors

Clostridium ljungdahlii (C. ljungdahlii, CLJU) is natively endowed producing acetic acid, 2,3-butandiol, and ethanol consuming gas mixtures of CO2, CO, and H2 (syngas). Here, we present the syngas-based isobutanol formation using C. ljungdahlii harboring the recombinant amplification of the “Ehrlich” pathway that converts intracellular KIV to isobutanol. Autotrophic isobutanol production was studied analyzing two different strains in 3-L gassed and stirred bioreactors. Physiological characterization was thoroughly applied together with metabolic profiling and flux balance analysis. Thereof, KIV and pyruvate supply were identified as key “bottlenecking” precursors limiting preliminary isobutanol formation in CLJU[KAIA] to 0.02 g L–1. Additional blocking of valine synthesis in CLJU[KAIA]:ilvE increased isobutanol production by factor 6.5 finally reaching 0.13 g L–1. Future metabolic engineering should focus on debottlenecking NADPH availability, whereas NADH supply is already equilibrated in the current generation of strains.

scholarly journals Metabolism as means for hypoxia adaptation: metabolic profiling and flux balance analysis

2009 ◽  
Vol 3 (1) ◽  
pp. 91 ◽  
Author(s):  
Jacob D Feala ◽  
Laurence Coquin ◽  
Dan Zhou ◽  
Gabriel G Haddad ◽  
Giovanni Paternostro ◽  
...  
Keyword(s):  
Flux Balance Analysis ◽  
Metabolic Profiling ◽  
Flux Balance ◽  
Hypoxia Adaptation ◽  
Balance Analysis

Dynamic flux balance analysis of biomass and lipid production by Antarctic thraustochytrid Oblongichytrium sp. RT2316‐13

2020 ◽  
Vol 117 (10) ◽  
pp. 3006-3017 ◽  
Author(s):  
Carolina Shene ◽  
Paris Paredes ◽  
Liset Flores ◽  
Allison Leyton ◽  
Juan A. Asenjo ◽  
...  
Keyword(s):  
Flux Balance Analysis ◽  
Lipid Production ◽  
Dynamic Flux Balance Analysis ◽  
Flux Balance ◽  
Balance Analysis

scholarly journals Understanding the host-microbe interactions using metabolic modeling

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jack Jansma ◽  
Sahar El Aidy
Keyword(s):  
Human Health ◽  
Flux Balance Analysis ◽  
Bacterial Species ◽  
Flux Balance ◽  
Interaction Field ◽  
In Silico Simulation ◽  
Balance Analysis ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Genome Scale

AbstractThe human gut harbors an enormous number of symbiotic microbes, which is vital for human health. However, interactions within the complex microbiota community and between the microbiota and its host are challenging to elucidate, limiting development in the treatment for a variety of diseases associated with microbiota dysbiosis. Using in silico simulation methods based on flux balance analysis, those interactions can be better investigated. Flux balance analysis uses an annotated genome-scale reconstruction of a metabolic network to determine the distribution of metabolic fluxes that represent the complete metabolism of a bacterium in a certain metabolic environment such as the gut. Simulation of a set of bacterial species in a shared metabolic environment can enable the study of the effect of numerous perturbations, such as dietary changes or addition of a probiotic species in a personalized manner. This review aims to introduce to experimental biologists the possible applications of flux balance analysis in the host-microbiota interaction field and discusses its potential use to improve human health.

scholarly journals A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fernando Santos-Beneit ◽  
Vytautas Raškevičius ◽  
Vytenis A. Skeberdis ◽  
Sergio Bordel
Keyword(s):  
Literature Search ◽  
Metabolic Modeling ◽  
Bioactive Molecules ◽  
Flux Balance ◽  
Triacsin C ◽  
Protein Palmitoylation ◽  
Positive Sense ◽  
Different Types ◽  
Balance Analysis ◽  
Docking Calculations

AbstractIn this study we have developed a method based on Flux Balance Analysis to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19. A literature search was carried out in order to identify suitable inhibitors of these enzymes, which were confirmed by docking calculations. In total, 10 targets and 12 bioactive molecules have been predicted. Among the most promising molecules we identified Triacsin C, which inhibits ACSL3, and which has been shown to be very effective against different viruses, including positive-sense single-stranded RNA viruses. Similarly, we also identified the drug Celgosivir, which has been successfully tested in cells infected with different types of viruses such as Dengue, Zika, Hepatitis C and Influenza. Finally, other drugs targeting enzymes of lipid metabolism, carbohydrate metabolism or protein palmitoylation (such as Propylthiouracil, 2-Bromopalmitate, Lipofermata, Tunicamycin, Benzyl Isothiocyanate, Tipifarnib and Lonafarnib) are also proposed.

scholarly journals Why does yeast ferment? A flux balance analysis study

2010 ◽  
Vol 38 (5) ◽  
pp. 1225-1229 ◽  
Author(s):  
Evangelos Simeonidis ◽  
Ettore Murabito ◽  
Kieran Smallbone ◽  
Hans V. Westerhoff
Keyword(s):  
Flux Balance Analysis ◽  
Energy Cost ◽  
Yeast Fermentation ◽  
Minimal Amount ◽  
Aerobic Growth ◽  
Analysis Study ◽  
Flux Balance ◽  
Balance Analysis ◽  
Genome Scale ◽  
Excess Glucose

Advances in biological techniques have led to the availability of genome-scale metabolic reconstructions for yeast. The size and complexity of such networks impose limits on what types of analyses one can perform. Constraint-based modelling overcomes some of these restrictions by using physicochemical constraints to describe the potential behaviour of an organism. FBA (flux balance analysis) highlights flux patterns through a network that serves to achieve a particular objective and requires a minimal amount of data to make quantitative inferences about network behaviour. Even though FBA is a powerful tool for system predictions, its general formulation sometimes results in unrealistic flux patterns. A typical example is fermentation in yeast: ethanol is produced during aerobic growth in excess glucose, but this pattern is not present in a typical FBA solution. In the present paper, we examine the issue of yeast fermentation against respiration during growth. We have studied a number of hypotheses from the modelling perspective, and novel formulations of the FBA approach have been tested. By making the observation that more respiration requires the synthesis of more mitochondria, an energy cost related to mitochondrial synthesis is added to the FBA formulation. Results, although still approximate, are closer to experimental observations than earlier FBA analyses, at least on the issue of fermentation.

Critical assessment of genome-scale metabolic models of Arabidopsis thaliana

2022 ◽  
Author(s):  
Javad Zamani ◽  
Sayed-Amir Marashi ◽  
Tahmineh Lohrasebi ◽  
Mohammad-Ali Malboobi ◽  
Esmail Foroozan
Keyword(s):  
Arabidopsis Thaliana ◽  
Flux Balance Analysis ◽  
Critical Assessment ◽  
Flux Balance ◽  
Balance Analysis ◽  
Metabolic Models ◽  
Living Organisms ◽  
Genome Scale

Genome-scale metabolic models (GSMMs) have enabled researchers to perform systems-level studies of living organisms. As a constraint-based technique, flux balance analysis (FBA) aids computation of reaction fluxes and prediction of...

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