FBA-BASED PREDICTION of BIOMASS and ETHANOL CONCENTRATION TIME PROFILES in Saccharomyces Cerevisiae FED-BATH CULTURES

Abstract

A Flux Balance Analysis (FBA)-based dynamical model is proposed for predicting biomass and ethanol concentration time profiles in Saccharomyces cerevisiae fed-batch cultures, with glucose and ammonium uptake rates as inputs. It is based on a metabolic network compiling the necessary internal fluxes for reproducing respiratory as well as respiro-fermentative metabolisms. While the objective cost function classically accounts for biomass growth maximization, additional linear constraints are used to reproduce overflow metabolism phenomena. New conditional equality constraints are introduced in the FBA linear programs to account for variable biomass composition (based on protein mass fraction identification with or without ammonium feeding). The proposed FBA-based model contains only 7 parameters which are estimated with the experimental data. A two-step procedure for separately solving the FBA linear programs and the macroscopic mass balance ODEs significantly lowers the computational load for parameter identification. Direct and leave-one-out cross-validation results are provided.