Parameter estimation in metabolic flux balance models for batch fermentation – formulation & solution using differential variational inequalities

Recent years have witnessed a surge in research in cellular biology. There has been particular interest in the interaction between cellular metabolism and its environment. In this work we present a framework for fitting fermentation models that include this interaction. Differential equations describe the evolution of extracellular metabolites, while a Linear Program models cell metabolism, and piecewise smooth functions model the links between cell metabolism and its environment. We show that the fermentation dynamics can be described using Differential Variational Inequalities (DVIs). Discretization of the system and reformulation of the VIs using optimality conditions converts the DVI to a Mathematical Program with Complementarity Constraints (MPCC). We briefly describe an interior point algorithm for solving MPCCs. Encouraging numerical results are presented in estimating model parameters to fit model prediction and data obtained from fermentation, using cultures of Saccharomyces cerevisiae reported in the literature.