ONLINE METABOLIC PATHWAY ANALYSIS BASED ON METABOLIC SIGNAL FLOW DIAGRAM

In this work, an integrated modeling approach based on a metabolic sig nal flow diagram and cellular energetics was used to model the metabol ic pathway analysis for the cultivation of yeast on glucose. This appr oach enables us to make a clear analysis of the flow direction of the carbon fluxes in the metabolic pathways as well as of the degree of ac tivation of a particular pathway for the synthesis of biomaterials for cell growth. The analyses demonstrate that the main metabolic pathway s of Saccharomyces cerevisiae change significantly during batch cultur e. Carbon flow direction is toward glycolysis to satisfy the increase of requirement for precursors and energy. The enzymatic activation of TCA cycle seems to always be at normal level, which may result in the overflow of ethanol due to its limited capacity. The advantage of this approach is that it adopts both virtues of the metabolic signal flow diagram and the simple network analysis method, focusing on the invest igation of the flow directions of carbon fluxes and the degree of acti vation of a particular pathway or reaction loop. All of the variables used in the model equations were determined an-line; the information o btained from the calculated metabolic coefficients may result in a bet ter understanding of cell physiology and help to evaluate the state of the cell culture process. (C) 1998 John Wiley & Sons, Inc.