A CCM-based modular and hybrid kinetic model to simulate the tryptophan synthesis in a fed-batch bioreactor using modified E. coli cells

Abstract

This paper presents a novel methodology to develop complex structured bi-level (hybrid) kinetic models of some important cell bioprocesses. The approached case study refers to the tryptophan (TRP) synthesis in E. coli cells. The required experimental data were collected from a fed-batch bioreactor (FBR). The developed structured kinetic model includes several inter-connected reaction pathway (modules) able to simulate the kinetics of glycolysis, TRP-operon expression, ATP-recovery system, all belonging to the central carbon metabolism (CCM). Experiments were carried out by using an E. coli strain modified to replace the PTS-system with a more efficient one to uptake the glucose (GLC) from the environment. By linking the FBR macroscopic state variables with the nano-scale variables describing the cell metabolic processes of interest, the resulted structured hybrid dynamic model presents a large number of advantages, such as: allows further in-silico (model-based) more accurate engineering developments; it can be used for bioinformatics purposes.