Possibilistic validation of a constraint-based model under data Scirccity: application to Pichia pastoris cultures

Constraint-based modelling allows building structured models of cells without accounting for intracellular kinetics. These models can be combined with experimental data to estimate the (pseudo-steady) state or phenotype exhibited by cells at given conditions, standing out as a useful analytical tool. In this work, a simplified, constraint-based model of Pichia pastoris, a widely recognized platform for recombinant protein expression, is derived from its metabolic network. Then, the model is validated against experimental data provided by different research groups: possibility theory is used to analyse the consistency between model and measurements. Afterwards, the biomass growth rate is estimated to illustrate the ability of the model to predict non-measured fluxes. The approach followed in this contribution is particularly useful in scenarios lacking data; it makes it possible to link the extracellular behaviour of Pichia pastoris during cultivation with its internal state, being a promising tool for optimization and monitoring industrial processes.