Metabolic Engineering by L. Eggeling, H. Sahm, A. A. de Graaf (auth.), H. Sahm, C.

By L. Eggeling, H. Sahm, A. A. de Graaf (auth.), H. Sahm, C. Wandrey (eds.)

Contents:L. Eggeling, H. Sahm, A.A. de Graaf: Quantifying and Directing Metabolite Flux: program to Amino Acid Overproduction.-
R. Krämer: research and Modeling of Substrate Uptake and Product unencumber by way of Prokaryotic and Eukaryotic Cells.-
D. Weuster-Botz, A.A. de Graaf: response Engineering tips on how to learn Intracellular Metabolite Concentrations.-
W. Wiechert, A.A. de Graaf: In Vivo desk bound Flux research by means of 13C Labeling Experiments.-
B. Sonnleitner: New ideas for Quantitative Bioprocess examine and Development.

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32 34 35 39 41 45 47 48 50 51 54 57 58 58 60 62 65 70 71 Translocation of molecules and ions across cell m e m b r a n e s is an important step for a complete description of the metabolic network in terms of kinetics, energetics and control. With a few exceptions, most molecules cross the permeability barrier of the m e m b r a n e with the aid of membrane-embedded carrier proteins. Uptake of nutrients (carbon, energy a n d nitrogen sources as wel~ as supplements) and excretion of the majority of products are thus carrier-mediated transport processes.

Glutamicum, export is apparently a new reaction to be considered, limiting the accumulation process. Further flux directioning for threonine overproduction requires biochemical and molecular studies on its excretion. Of course strains with high flux towards threonine are ideally suited to enable further flux directioning towards isoleucine. For this purpose feedback-resistant mutant enzymes of the threonine dehydratase of C. ylutamicum were generated [125]. The influence of four different ilvA alleles (threonine dehydratase genes) in vectors of high and low copy number on isoleucine accumulation was quantified in strains with feedback-resistant homoserine dehydrogenase [54].

G. binding protein-dependent transport systems and phosphoenolpyruvate:sugar phosphotransferase systems. e. g. some ATPases. It is now widely accepted that transport systems should be classified according to the concept introduced by Mitchell [2], based on the utilization of energy sources for transport. The different classes are briefly outlined here (Fig. 2) and the driving forces responsible for the vectorial process of translocation are summarized (Fig. 3). For a more detailed description the reader is referred to other reviews and books on this topic [1, 3-7].

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