Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli
Abstract To which extent can optimality principles describe the operation of metabolic networks? By explicitly considering experimental errors and in silico alternate optima in flux balance analysis, we systematically evaluate the capacity of 11 objective functions combined with eight adjustable con...
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| Format: | Article |
| Language: | English |
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Springer Nature
2007-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb4100162 |
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| _version_ | 1849225741840941056 |
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| author | Robert Schuetz Lars Kuepfer Uwe Sauer |
| author_facet | Robert Schuetz Lars Kuepfer Uwe Sauer |
| author_sort | Robert Schuetz |
| collection | DOAJ |
| description | Abstract To which extent can optimality principles describe the operation of metabolic networks? By explicitly considering experimental errors and in silico alternate optima in flux balance analysis, we systematically evaluate the capacity of 11 objective functions combined with eight adjustable constraints to predict 13C‐determined in vivo fluxes in Escherichia coli under six environmental conditions. While no single objective describes the flux states under all conditions, we identified two sets of objectives for biologically meaningful predictions without the need for further, potentially artificial constraints. Unlimited growth on glucose in oxygen or nitrate respiring batch cultures is best described by nonlinear maximization of the ATP yield per flux unit. Under nutrient scarcity in continuous cultures, in contrast, linear maximization of the overall ATP or biomass yields achieved the highest predictive accuracy. Since these particular objectives predict the system behavior without preconditioning of the network structure, the identified optimality principles reflect, to some extent, the evolutionary selection of metabolic network regulation that realizes the various flux states. |
| format | Article |
| id | doaj-art-08a1ba2036b84e48b29f60d3ad45bcfb |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2007-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-08a1ba2036b84e48b29f60d3ad45bcfb2025-08-24T12:01:53ZengSpringer NatureMolecular Systems Biology1744-42922007-07-013111510.1038/msb4100162Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coliRobert Schuetz0Lars Kuepfer1Uwe Sauer2Institute of Molecular Systems Biology, ETHInstitute of Molecular Systems Biology, ETHInstitute of Molecular Systems Biology, ETHAbstract To which extent can optimality principles describe the operation of metabolic networks? By explicitly considering experimental errors and in silico alternate optima in flux balance analysis, we systematically evaluate the capacity of 11 objective functions combined with eight adjustable constraints to predict 13C‐determined in vivo fluxes in Escherichia coli under six environmental conditions. While no single objective describes the flux states under all conditions, we identified two sets of objectives for biologically meaningful predictions without the need for further, potentially artificial constraints. Unlimited growth on glucose in oxygen or nitrate respiring batch cultures is best described by nonlinear maximization of the ATP yield per flux unit. Under nutrient scarcity in continuous cultures, in contrast, linear maximization of the overall ATP or biomass yields achieved the highest predictive accuracy. Since these particular objectives predict the system behavior without preconditioning of the network structure, the identified optimality principles reflect, to some extent, the evolutionary selection of metabolic network regulation that realizes the various flux states.https://doi.org/10.1038/msb410016213C-fluxevolutionflux balance analysismetabolic networknetwork optimality |
| spellingShingle | Robert Schuetz Lars Kuepfer Uwe Sauer Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli Molecular Systems Biology 13C-flux evolution flux balance analysis metabolic network network optimality |
| title | Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli |
| title_full | Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli |
| title_fullStr | Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli |
| title_full_unstemmed | Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli |
| title_short | Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli |
| title_sort | systematic evaluation of objective functions for predicting intracellular fluxes in escherichia coli |
| topic | 13C-flux evolution flux balance analysis metabolic network network optimality |
| url | https://doi.org/10.1038/msb4100162 |
| work_keys_str_mv | AT robertschuetz systematicevaluationofobjectivefunctionsforpredictingintracellularfluxesinescherichiacoli AT larskuepfer systematicevaluationofobjectivefunctionsforpredictingintracellularfluxesinescherichiacoli AT uwesauer systematicevaluationofobjectivefunctionsforpredictingintracellularfluxesinescherichiacoli |