A simple metabolic flux balance analysis of biomass and bioethanol Production in Saccharomyces cerevisiae fed-batch cultures

Production of Saccharomyces cerevisiae yeast for applications in the food industry or in bioethanol production still presents important techno-economic challenges as an industrial bioprocess. Mathematical modeling of cellular metabolism in biological production usually improves process yields, though for industrial applications, the model should be as simple as possible in order to sustain model usefulness and technical feasibility. A comparative analysis between a black box description and a simple metabolic network accounting for the main metabolic events involved in yeast growth and bioethanol production is proposed here. In both cases, a thorough analysis of reaction rates allowed for the ethanol concentrations produced in fed-batch yeast cultures, although our results showed more accurate estimations with the metabolic flux balance methodology. Moreover, an interpretation of the yeast physiological state in fed-batch cultures at different glucose feed concentrations was accomplished by means of a stoichiometric analysis linked to the simplified metabolic network. The results confirmed that increasing glucose uptake rates, controlled mainly by the glucose concentration in the input flow, produced an up-regulation in reductive catabolism, resulting in higher ethanol excretion. The biomass production relied mostly on oxidative catabolism, which is controlled by the glucose and oxygen uptake rates. Thus, ethanol or biomass production is strongly dependent on the physiological state of yeast in the culture, which can be inferred from a suitable metabolic flux balance approach.