Abstract
The aim of understanding the metabolism of the cell in order to derive how high-level product formation can be achieved has led to astonishing progress with respect to the in vivo quantification of carbon fluxes and the quantification of flux control. This quantification usually holds only for one specific flux situation thus requiring additional approaches in order to obtain indications of how to produce a flux increase of relevance useful for overproduction. This is in part due to the complex responses of cells to high flux increases, including altered gene expression, alteration of energy metabolism, or accumulation of toxic intermediates, thus preventing a quantitative prediction of the targets to be altered. Instead, experimental techniques have to be used to examine the resulting consequences for each individual example. Currently, it is being found that branching points in biosynthesis, precursor supply in fueling reactions, and export of metabolites deserve particular attention in order to increase metabolite flux. By applying molecular techniques, to such selected targets of the l-lysine and l-isoleucine biosynthesis of Corynebacterium glutamicum., high amino acid overproduction can be obtained with this bacterium.
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Eggeling, L., Sahm, H., de Graaf, A.A. (1996). Quantifying and directing metabolite flux: Application to amino acid overproduction. In: Sahm, H., Wandrey, C. (eds) Metabolic Engineering. Advances in Biochemical Engineering/Biotechnology, vol 54. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0102331
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