In silico Determination of Some Conditions Leading to Glycolytic Oscillations and Their Interference With Some Other Processes in E. coli Cells

Abstract

Autonomous oscillations of species levels in the glycolysis express the self-control of this essential cellular pathway belonging to the central carbon metabolism (CCM), and this phenomenon takes place in a large number of bacteria. Oscillations of glycolytic intermediates in living cells occur according to the environmental conditions and to the cell characteristics, especially the adenosine triphosphate (ATP) recovery system. Determining the conditions that lead to the occurrence and maintenance of the glycolytic oscillations can present immediate practical applications. Such a model-based analysis allows in silico (model-based) design of genetically modified microorganisms (GMO) with certain characteristics of interest for the biosynthesis industry, medicine, etc. Based on our kinetic model validated in previous works, this paper aims to in silico identify operating parameters and cell factors leading to the occurrence of stable glycolytic oscillations in the Escherichia coli cells. As long as most of the glycolytic intermediates are involved in various cellular metabolic pathways belonging to the CCM, evaluation of the dynamics and average level of its intermediates is of high importance for further applicative analyses. As an example, by using a lumped kinetic model for tryptophan (TRP) synthesis from literature, and its own kinetic model for the oscillatory glycolysis, this paper highlights the influence of glycolytic oscillations on the oscillatory TRP synthesis through the PEP (phosphoenolpyruvate) glycolytic node shared by the two oscillatory processes. The numerical analysis allows further TRP production maximization in a fed-batch bioreactor (FBR).