A STRUCTURED APPROACH FOR SELECTION AMONG CANDIDATE METABOLIC NETWORKMODELS AND ESTIMATION OF UNKNOWN STOICHIOMETRIC COEFFICIENTS

A metabolic network model is one of the cornerstones of the emerging M etabolic Engineering methodology. In this article, special attention i s therefore, given to the phase of model building. A five-stage struct ured approach to metabolic network modeling is introduced. The basic s teps are: (1) to collect a priori knowledge on the reaction network an d to build candidate network models, (2) to perform an a priori check of the model, (3) to estimate the unknown parameters in the model, (4) to check the identified model for acceptability from a biological and thermodynamic point of view, and (5) to validate the model with new d ata. The approach is illustrated with a growth system involving baker' s yeast growing on mixtures of substrates. Special attention is given to the central uncertainties in metabolic network modeling, i.e., esti mation of energetic parameters in the network and the choice of the so urce of anabolic reducing equivalents NADPH. (C) 1998 John Wiley & Son s, Inc.