A generalized NURBS based dynamic metabolic flux analysis framework: deciphering intracellular pathway activation from extracellular measurements

摘要

Current macroscopic population balance models are not sufficient to obtain a profound understanding in the complex behaviour of microbial responses in food. Including metabolic network information in mathematical models leads to an improved mechanistic insight in microbial processes. The main difficulty in including such information is the high number of fluxes and metabolites and the number of ordinary differential equations that has to be added to the model equations. To reduce the number of mass balance differential equations, pseudo steady state is assumed and the intracellular mass balances are replaced by an underdetermined system of algebraic equations. Dynamic metabolic flux analysis estimates intracellular time-dependent flux distributions from available measurements, by parameterizing the fluxes as a function of time. In this article, a novel DMFA technique based on a non-uniform rational B-splines (NURBS) parameterization of the free fluxes (NDMFA) is presented. This NDMFA technique can be seen as a generalization of previously introduced state of the art DMFA techniques.