Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli Export

@article{citeulike:1449780, 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.}, author = {Schuetz, Robert and Kuepfer, Lars and Sauer, Uwe}, citeulike-article-id = {1449780}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/msb4100162}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/msb4100162}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17625511}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17625511}, day = {10}, doi = {10.1038/msb4100162}, journal = {Molecular Systems Biology}, keywords = {flux\_balance\_analysis}, month = {July}, pages = {119+}, posted-at = {2007-10-01 06:42:59}, priority = {2}, publisher = {Nature Publishing Group}, title = {Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli}, url = {http://dx.doi.org/10.1038/msb4100162}, volume = {3}, year = {2007} }

TY - JOUR ID - citeulike:1449780 L3 - citeulike-article-id:1449780 N2 - 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. JF - Molecular Systems Biology TI - Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli PB - Nature Publishing Group VL - 3 SP - 119 KW - flux_balance_analysis AU - Schuetz, Robert AU - Kuepfer, Lars AU - Sauer, Uwe PY - 2007/07/10/ UR - http://dx.doi.org/10.1038/msb4100162 ER -