In silico optimization of a bioreactor with an E. coli culture for tryptophan production by using a structured model coupling the oscillating glycolysis and tryptophan synthesis

Abstract Tryptophan ( TRP ) is an aromatic non-polar α-amino-acid essential, whose biosynthesis maximization is of high practical importance in industry, and medicine. On one hand, it is to underline that TRP synthesis is an oscillatory process strongly connected to the glycolysis through the PEP (phosphoenolpyruvate) node. On the other hand, it is well-known that glycolysis, under certain environmental conditions, displays autonomous oscillations of the glycolytic intermediates’ concentrations thus reflecting the dynamics of the control and regulation of this major catabolic pathway with a major role in the cell central carbon metabolism ( CCM ) in living cells. Consequently, glycolysis model is the ‘core’ module of any systematic and structured model-based analysis of most of metabolic sub-process. By coupling two adequate reduced kinetic models for the glycolysis and TRP synthesis in the E. coli cells, adopted from literature, with the model of a semi-continuous bioreactor, this paper derives, for the first time, an in silico analysis of the optimal operating conditions of the bioreactor used for tryptophan synthesis, with accounting for the two interfering oscillatory processes.