Modeling metabolic systems: the need for dynamics

Living organisms exhibit dynamic shifts of metabolic pathways to cope with various perturbations. Such temporal change of modus operandi is one of the key mechanisms characterizing metabolic behavior. In this review, we highlight the importance and potential of dynamic modeling in understanding and harnessing metabolic systems, in particular, for bioprocess optimization and metabolic engineering. In a field that harbors a variety of approaches, their relative assessment calls for appropriate quantitative measures. Toward this, we present rational criteria for the evaluation of metabolic models, and recent advances in dynamic modeling that include accounting for dynamic regulation at the whole network level, development of frameworks able to handle large-scale networks on the basis of pathway analysis, and whole-cell modeling of a simple microbe.