Central Carbon Metabolism

Today the metabolic network of the central metabolism of C. glutamicum involving glycolysis, pentose phosphate pathway (PPP), TCA cycle as well as anaplerotic and gluconeogenetic reactions is well known (Fig. 1). Different enzymes are involved in the interconversion of carbon between TCA cycle (malate/oxaloacetate) and glycolysis (pyruvate/phosphoenolpyruvate). For anaplerotic replenishment of the TCA cycle, C. glutamicum exhibits pyruvate carboxylase [20] and phosphoenol-pyruvate (PEP) carboxylase as carboxylating enzymes. Malic enzyme [21] and PEP carboxykinase [22,23] catalyze decarboxylation reactions from the TCA cycle 

---

This is not the place to expose in detail the problems and the solutions already obtained in studying biochemical reaction networks. However, because of the importance of this problem and the great recent interest in understanding metabolic networks, we hope to throw a little light on this area. Figure 10.3-23 shows a model for the metabolic pathways involved in the central carbon metabolism of Escherichia coli through glycolysis and the pentose phosphate pathway [22]. 

C. Chassagnole, N. Noisommit Rizzi, J. W. Schmid, K. Mauch, and M. Reuss, Dynamic modeling of the central carbon metabolism of Escherichia coli. Biotechnol. Bioeng. 79(1), 53 73 (2002). 

G. Sriram, D. B. Fulton, and J. V. Shanks, Flux quantification in central carbon metabolism of Catharanthus roseus hairy roots by 13c labeling and comprehensive bondomer balancing. Phytochemistry 68, 2243 2257 (2007). 

Sauer, U., Lasko, D. R., Fiaux, J., Hochuli, M., Glaser, R., Szyperski, T., Wuthrich, K., and Bailey, J. E. (1999). Metabolic flux ratio analysis of genetic and environmental modulations of Escherichia coli central carbon metabolism. J. Bacteriol, 181(21), 6679-6688. 

Metabolic flux analysis using isotope labelling methods has been recently applied to the characterisation of several B. megaterium strains [87, 88], The determination of the isotope labelling of the amino acids was carried out with GC-MS. Fluxes of the central carbon metabolism were estimated following the labelling pattern of the amino acids from their precursors. 

Timischl, B., Dettmer, K., and Oefner, P.J. Mass spectrometry in the analysis of the central carbon metabolism. Anal. Bioanal. Chem. 2008, 391, 895-898. 

Fig. 13.1 Central carbon metabolism of Escherichia coli. See Section 13.2 for details.

Cultivation of RB50 [pRF69] with fractional C-labeled glucose as carbon source and metabolic flux balancing indicated that riboflavin formation in this strain was still limited by the fluxes through the terminal biosynthetic rather than the central carbon metabolic pathways. To debottleneck the riboflavin biosynthetic pathway further, a similar approach as described above was applied to introduce a second P poz-driven and amplifiable rib expression cassette linked to a tetracycline resistance marker at the bpr locus (map position... 

Fig. 3.1 CE-MS analysis of Bacillus subtilis extracts. Ion electropherograms are shown for selected intermediates of central carbon metabolism, energy eqnivalents, and redox cofactors. Separation was achieved in the negative mode by CZE in coated capillaries with reversed inner-wall polarity. (Reprinted with permission from [127].)...

Fischer, E. Sauer, U. Metabohc flux profihng of Escherichia coli mutants in central carbon metabolism using GC-MS. Eur. J. Biochem. 2003, 270, 880-891. 

U., Pfliiger-Grau, K., and de Lorenzo, V. (2012) Regulatory tasks of the phosphoenolpyruvate-phosphotransferase system of Pseudomonas putida in central carbon metabolism. mBio, 3 (2), e00028-12. 

L.M., Siemann-Herzberg, M., and Schmid, A. (2014) The functional structure of central carbon metabolism in Pseudomonas putida KT2440. 

Bolten, C.J., Heinzle, E., Muller, R., and Wittmann, C. (2009) Investigation of the central carbon metabolism of Sorangium cellulosum metabolic network reconstruction and quantification of pathway fluxes. /. Microbiol. Biotechnol, 19 (1), 23-36. 

Daran-Lapujade, R, Jansen, M. L. A., Daran, J.-M., van Gulik, W., de Winde, J. H., Pronk, J. T. (2003). Role of transcriptional regulation in controlling fluxes in central carbon metabolism of Saccharomyces cerevisiae, a chemostat study. Journal of Biological Chemistry, 91, 9125-9138. 

---