title: Current state and challenges for dynamic metabolic modeling.
abstract: While the stoichiometry of metabolism is probably the best studied cellular level, the dynamics in metabolism can still not be well described, predicted and, thus, engineered. Unknowns in the metabolic flux behavior arise from kinetic interactions, especially allosteric control mechanisms. While the stoichiometry of enzymes is preserved in vitro, their activity and kinetic behavior differs from the in vivo situation. Next to this challenge, it is infeasible to test the interaction of each enzyme with each intracellular metabolite in vitro exhaustively. As a consequence, the whole interacting metabolome has to be studied in vivo to identify the relevant enzymes properties. In this review we discuss current approaches for in vivo perturbation experiments, that is, stimulus response experiments using different setups and quantitative analytical approaches, including dynamic carbon tracing. Next to reliable and informative data, advanced modeling approaches and computational tools are required to identify kinetic mechanisms and their parameters.
authors.affiliation: Department of Biotechnology, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands.
authors.forename: Eleni
authors.initials: E
authors.lastname: Vasilakou
authors.affiliation: Institute for Biotechnology and Bioengineering, University of Minho, Braga, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Machado
authors.affiliation: Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425 Jülich, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Theorell
authors.affiliation: Institute for Biotechnology and Bioengineering, University of Minho, Braga, Portugal; SilicoLife, Braga, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rocha
authors.affiliation: Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425 Jülich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Nöh
authors.affiliation: Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425 Jülich, Germany; Institute of Biotechnology, RWTH Aachen University, Worringer Weg 1, D-52056 Aachen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Oldiges
authors.affiliation: Department of Biotechnology, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands. Electronic address: s.a.wahl@tudelft.nl.
authors.forename: S Aljoscha
authors.initials: SA
authors.lastname: Wahl
mesh_terms: D019295:Computational Biology / Q000379:methods; D004926:Escherichia coli / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D055442:Metabolome; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000378:metabolism*