A Systematic Modeling Approach to Elucidate the Triggering of the Stringent Response in Recombinant E. coli Systems
A hybrid modeling approach, combining a stoichiometric model of the E. coli metabolic network and kinetic-based descriptions for the production of recombinant protein, cell growth and ppGpp synthesis, was applied to describe metabolic bottlenecks associated with recombinant processes. The model represents the triggering of the stringent response upon the deprivation of amino acids caused by the additional drainage of biosynthetic precursors for the production of recombinant proteins. The equation for ppGpp synthesis allows to estimate the accumulation of this molecule above its basal levels once amino acid shortages occur. The capability to predict these stress-responsive events might be crucial in the design of optimal cultivation strategies.
KeywordsRecombinant Protein Production Flux Balance Analysis Amino Acid Pool Stringent Response Intracellular Amino Acid
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- 3.Hoffmann, F., Rinas, U.: Stress induced by recombinant protein production in Escherichia coli. Advances in Biochemical Engineering / Biotechnology 89, 73–92 (2004)Google Scholar
- 4.Jain, V., Kumar, M., Chatterji, D.: ppGpp: Stringent response and survival. Journal of Microbiology 44(1), 1–10 (2006)Google Scholar
- 5.Mukherjee, T.K., Raghavan, A., Chatterji, D.: Shortage of nutrients in bacteria: The stringent response. Current Science 75(7), 684–689 (1998)Google Scholar
- 6.Neidhardt, F.C., Ingraham, J.L., Schaechter, M.: Physiology of the bacterial cell - a molecular approach. Sinauer Associates, Sunderland, USA (1990)Google Scholar
- 12.Torok, I., Kari, C.: Accumulation of pp Gpp in a rel A mutant of Escherichia coli during amino acid starvation. Journal of Biological Chemistry 255(9), 3838–3840 (1980)Google Scholar
- 13.Varma, A., Palsson, B.O.: Metabolic Flux Balancing - Basic Concepts, Scientific and Practical Use. Bio-Technology 12(10), 994–998 (1994)Google Scholar