Abstract：
:(13)C metabolic flux analysis (MFA) has become an important and powerful tool for the quantitative analysis of metabolic networks in the framework of metabolic engineering. Isotopically instationary (13)C MFA under metabolic stationary conditions is a promising refinement of classical stationary MFA. It accounts for the experimental requirements of non-steady-state cultures as well as for the shortening of the experimental duration. This contribution extends all computational methods developed for classical stationary (13)C MFA to the instationary situation by using high-performance computing methods. The developed tools allow for the simulation of instationary carbon labeling experiments (CLEs), sensitivity calculation with respect to unknown parameters, fitting of the model to the measured data, statistical identifiability analysis and an optimal experimental design facility. To explore the potential of the new approach all these tools are applied to the central metabolism of Escherichia coli. The achieved results are compared to the outcome of the stationary counterpart, especially focusing on statistical properties. This demonstrates the specific strengths of the instationary method. A new ranking method is proposed making both an a priori and an a posteriori design of the sampling times available. It will be shown that although still not all fluxes are identifiable, the quality of flux estimates can be strongly improved in the instationary case. Moreover, statements about the size of some immeasurable pool sizes can be made.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Nöh K,Wahl A,Wiechert Wdoi
10.1016/j.ymben.2006.05.006subject
Has Abstractpub_date
2006-11-01 00:00:00pages
554-77issue
6eissn
1096-7176issn
1096-7184pii
S1096-7176(06)00044-9journal_volume
8pub_type
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