Dynamic metabolic flux analysis of underdetermined and overdetermined metabolic networks

In this work, two metabolic networks representing the metabolism of CHO cells in fed-batch cultures are considered. The first metabolic network is relatively detailed and underdetermined with the available extracellular measurements, while the second is a reduced version of the former and is overdetermined. A dynamic metabolic flux analysis based on convex analysis (DMFCA) is applied to the detailed network, which allows the computation of the time evolution of bounded intervals. On the other hand, a linear optimization problem is solved for the reduced-size network, with either positivity constraints or box constraints inferred from DMFCA. In all cases, smoothing splines and mass balance differential equations are used to infer the time evolution of the uptake and excretion rates from experimental data. The analysis allows to get insight into CHO metabolism as well as to investigate the influence of the size of the metabolic network.