TY - JOUR
T1 - Current state and challenges for dynamic metabolic modeling
AU - Vasilakou, Eleni
AU - Machado, Daniel
AU - Theorell, Axel
AU - Rocha, Isabel
AU - Nöh, Katharina
AU - Oldiges, Marco
AU - Wahl, S. Aljoscha
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
UR - http://resolver.tudelft.nl/uuid:4359a9c2-cb04-4ec6-99df-a1455a5adc7a
UR - http://www.scopus.com/inward/record.url?scp=84979266959&partnerID=8YFLogxK
U2 - 10.1016/j.mib.2016.07.008
DO - 10.1016/j.mib.2016.07.008
M3 - Review article
AN - SCOPUS:84979266959
SN - 1369-5274
VL - 33
SP - 97
EP - 104
JO - Current Opinion in Microbiology
JF - Current Opinion in Microbiology
ER -