Time Integrated Flux Analysis: Exploiting the Concentration Measurements Directly for Cost-Effective Metabolic Network Flux Analysis
Abstract
:1. Introduction
2. Methods
2.1. Metabolic Time Integrated Flux Analysis
2.2. Time-Integrated Flux Balance/Variability Analysis
2.3. Sparse Time Integrated Flux Balance/Variability Analysis
2.4. Simulation Case I
2.4.1. Process Operation
2.4.2. Simulated Sampling Strategies and Noise Levels
2.5. Simulation Case II
2.5.1. Simulated Sampling Strategies and Noise Levels
2.5.2. Test Cases (Measured and Estimated Fluxes; Irreversible Reactions)
2.6. Experimental Case
3. Results
3.1. Simulation Case I
3.1.1. Quantitative Performance Assessment
3.1.2. Qualitative Performance Assessment
3.1.3. Comparison with MFA and Derivative Approach for Flux Estimation
3.2. Simulation Case II
3.2.1. Effect of Redundancy
3.2.2. Effect of Irreversibility Constrains
3.3. Experimental Case
3.3.1. Quantitative Performance Assessment
3.3.2. Qualitative Performance Assessment
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Appendix A. Simulation Case I
Appendix A.1. Network Topology
Appendix A.2. Simulated Kinetics
Variable/Parameter | Value | Comment |
---|---|---|
(initial) | 1 L | initial conditions |
(initial) | 2 | |
(initial) | 0.004 | |
(initial) | 15 | |
200 | feed characterization | |
0.05 L/h | After 8 h of fermentation | |
PARAMETERS | ||
0.005 | Controlled at 20% | |
0.05 | ||
0.1 | ||
0.04 | ||
0.1 | ||
0.07 | ||
0.1 | ||
0.06 | ||
0.1 | ||
0.01 | ||
0.1 | ||
0.04 | ||
0.2 | ||
0.2 | ||
0.1 | ||
0.01 | ||
0.0028 |
Appendix B. Simulation Case II
Appendix B. Network Topology and Simulation Kinetics
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Portela, R.M.C.; Richelle, A.; Dumas, P.; von Stosch, M. Time Integrated Flux Analysis: Exploiting the Concentration Measurements Directly for Cost-Effective Metabolic Network Flux Analysis. Microorganisms 2019, 7, 620. https://doi.org/10.3390/microorganisms7120620
Portela RMC, Richelle A, Dumas P, von Stosch M. Time Integrated Flux Analysis: Exploiting the Concentration Measurements Directly for Cost-Effective Metabolic Network Flux Analysis. Microorganisms. 2019; 7(12):620. https://doi.org/10.3390/microorganisms7120620
Chicago/Turabian StylePortela, Rui M. C., Anne Richelle, Patrick Dumas, and Moritz von Stosch. 2019. "Time Integrated Flux Analysis: Exploiting the Concentration Measurements Directly for Cost-Effective Metabolic Network Flux Analysis" Microorganisms 7, no. 12: 620. https://doi.org/10.3390/microorganisms7120620