Exploring the gap between dynamic and constraint-based models of metabolism.

TitleExploring the gap between dynamic and constraint-based models of metabolism.
Publication TypeJournal Article
Year of Publication2012
AuthorsMachado, D, Costa, RS, Ferreira, EC, Rocha, I, Tidor, B
JournalMetab Eng
Date Published2012 Mar
KeywordsCarbon, Escherichia coli, Kinetics, Models, Biological

Systems biology provides new approaches for metabolic engineering through the development of models and methods for simulation and optimization of microbial metabolism. Here we explore the relationship between two modeling frameworks in common use namely, dynamic models with kinetic rate laws and constraint-based flux models. We compare and analyze dynamic and constraint-based formulations of the same model of the central carbon metabolism of Escherichia coli. Our results show that, if unconstrained, the space of steady states described by both formulations is the same. However, the imposition of parameter-range constraints can be mapped into kinetically feasible regions of the solution space for the dynamic formulation that is not readily transferable to the constraint-based formulation. Therefore, with partial kinetic parameter knowledge, dynamic models can be used to generate constraints that reduce the solution space below that identified by constraint-based models, eliminating infeasible solutions and increasing the accuracy of simulation and optimization methods.

Alternate JournalMetab. Eng.
PubMed ID22306209
PubMed Central IDPMC3465724
Grant ListR01 GM065418-07 / GM / NIGMS NIH HHS / United States
U54 CA112967-07 / CA / NCI NIH HHS / United States