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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 621645, 19 pages
Research Article

Dynamic Metabolic Flux Analysis Demonstrated on Cultures Where the Limiting Substrate Is Changed from Carbon to Nitrogen and Vice Versa

1Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Coupure Links 653, 9000 Gent, Belgium
2Laboratory of Industrial Microbiology and Biocatalysis, Ghent University, Coupure Links 653, 9000 Gent, Belgium
3Département de Génie Civil et Génie des Eaux, Université Laval, Québec, QC, Canada G1V OA6

Received 23 November 2009; Revised 10 April 2010; Accepted 24 June 2010

Academic Editor: Maciek Antoniewicz

Copyright © 2010 Gaspard Lequeux et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The main requirement for metabolic flux analysis (MFA) is that the cells are in a pseudo-steady state, that there is no accumulation or depletion of intracellular metabolites. In the past, the applications of MFA were limited to the analysis of continuous cultures. This contribution introduces the concept of dynamic MFA and extends MFA so that it is applicable to transient cultures. Time series of concentration measurements are transformed into flux values. This transformation involves differentiation, which typically increases the noisiness of the data. Therefore, a noise-reducing step is needed. In this work, polynomial smoothing was used. As a test case, dynamic MFA is applied on Escherichia coli cultivations shifting from carbon limitation to nitrogen limitation and vice versa. After switching the limiting substrate from N to C, a lag phase was observed accompanied with an increase in maintenance energy requirement. This lag phase did not occur in the C- to N-limitation case.