Applied Microbiology and Biotechnology

, Volume 91, Issue 5, pp 1247–1265

The benefits of being transient: isotope-based metabolic flux analysis at the short time scale

Mini-Review

DOI: 10.1007/s00253-011-3390-4

Cite this article as:
Nöh, K. & Wiechert, W. Appl Microbiol Biotechnol (2011) 91: 1247. doi:10.1007/s00253-011-3390-4

Abstract

Metabolic fluxes are the manifestations of the co-operating actions in a complex network of genes, transcripts, proteins, and metabolites. As a final quantitative endpoint of all cellular interactions, the intracellular fluxes are of immense interest in fundamental as well as applied research. Unlike the quantities of interest in most omics levels, in vivo fluxes are, however, not directly measureable. In the last decade, 13C-based metabolic flux analysis emerged as the state-of-the-art technique to infer steady-state fluxes by data from labeling experiments and the use of mathematical models. A very promising new area in systems metabolic engineering research is non-stationary 13C-metabolic flux analysis at metabolic steady-state conditions. Several studies have demonstrated an information surplus contained in transient labeling data compared to those taken at the isotopic equilibrium, as it is classically done. Enabled by recent, fairly multi-disciplinary progress, the new method opens several attractive options to (1) generate new insights, e.g., in cellular storage metabolism or the dilution of tracer by endogenous pools and (2) shift limits, inherent in the classical approach, towards enhanced applicability with respect to cultivation conditions and biological systems. We review the new developments in metabolome-based non-stationary 13C flux analysis and outline future prospects for accurate in vivo flux measurement.

Keywords

Non-stationary 13C-metabolic flux analysis Transient isotope-labeling experiments Labeling time constants Metabolic networks Metabolic engineering Systems biology 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Institute of Bio- and Geosciences 1: Biotechnology 2Forschungszentrum Jülich GmbHJülichGermany