Validation and Optimization of a Yeast Dynamic Flux Balance Model using a Parallel Bioreactor System

Abstract

The availability of parallel fermentation systems comprised of miniature, independently controlled bioreactors provides new opportunities for high throughput bioprocess development. In this study, we demonstrated the use of a four bioreactor system to validate predictions from a dynamic flux balance model of Saccharomyces cerevisiae metabolism. First we showed that the four 250 mL bioreactors generated very reproducible aerobic batch culture data and that the parallel system results could be accurately scaled-up to a standard 1.25 L laboratory bioreactor by matching oxygen mass transfer coefficients in the different reactors. A S. cerevisiae dynamic flux balance model previously developed in our group was shown to produce anaerobic and aerobic batch profiles in excellent agreement with the parallel system. The validated model was used to determine the optimal aerobic-anaerobic switching time for maximal ethanol production in batch culture. An optimal switching time in agreement with parallel system experiments was obtained. We concluded that parallel fermentation is a powerful tool for batch culture optimization when used in conjunction with dynamic metabolic models.