Current state and challenges for dynamic metabolic modeling

Eleni Vasilakou, Daniel Machado, Axel Theorell, Isabel Rocha, Katharina Nöh, Marco Oldiges, S Aljoscha Wahl
2016 Current Opinion in Microbiology  
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
more » ... ction 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.
doi:10.1016/j.mib.2016.07.008 pmid:27472025 fatcat:yeerk4ahu5bxlaisjio57fgkne