From stationary to instationary metabolic flux analysis.

Metabolic flux analysis using 13C labeled substrates is an important tool for metabolic engineering. Although it has now been evolving for more than ten years, metabolic flux analysis has still not reached the limits of its application. Current developments aim at extending to instationary industrial production conditions like batch and fed-batch fermentations on the one hand, and at miniaturization and high throughput flux analysis on the other. In both cases, reducing the duration of the labeling experiment is of major interest. For that reason, there is now interest in the instationary transient of the 13C enrichment during a labeling experiment. This paper presents some recent developments in the field of instationary metabolic flux analysis and discusses some critical aspects and limitations using some simulation examples.