초록
<P><B>Background</B></P><P>A key step in any process that converts lignocellulose to biofuels is the efficient fermentation of both hexose and pentose sugars. The co-culture of respiratory-deficient <I>Saccharomyces cerevisiae</I> and wild-type <I>Scheffersomyces stipitis</I> has been identified as a promising system for microaerobic ethanol production because <I>S. cerevisiae</I> only consumes glucose while <I>S. stipitis</I> efficiently converts xylose to ethanol.</P><P><B>Results</B></P><P>To better predict how these two yeasts behave in batch co-culture and to optimize system performance, a dynamic flux balance model describing co-culture metabolism was developed from genome-scale metabolic reconstructions of the individual organisms. First a dynamic model was developed for each organism by estimating substrate uptake kinetic parameters from batch pure culture data and evaluating model extensibility to different microaerobic growth conditions. The co-culture model was constructed by combining the two individual models assuming a cellular objective of total growth rate maximization. To obtain accurate predictions of batch co-culture data collected at different microaerobic conditions, the <I>S. cerevisiae</I> maximum glucose uptake rate was reduced from its pure culture value to account for more efficient <I>S. stipitis</I> glucose uptake in co-culture. The dynamic co-culture model was used to predict the inoculum concentration and aeration level that maximized batch ethanol productivity. The model predictions were validated with batch co-culture experiments performed at the optimal conditions. Furthermore, the dynamic model was used to predict how engineered improvements to the <I>S. stipitis</I> xylose transport system could improve co-culture ethanol production.</P><P><B>Conclusions</B></P><P>These results demonstrate the utility of the dynamic co-culture metabolic model for guiding process and metabolic engineering efforts aimed at increasing microaerobic ethanol production from glucose/xylose mixtures.</P>