초록
<P><B>Abstract</B></P> <P>The recently engineered <I>Geobacillus thermoglucosidasius</I> strain is an industrially potent thermophilic ethanologen. We employ a systematic approach to improve our understanding of the fermentation process using cellobiose as the substrate. Dynamic metabolic flux analysis clearly shows that the fluxes from pyruvate to lactate and formate are both strictly constrained throughout the process and that both the maximum ethanol yield (0.46C/C) and the maximum specific productivity (19.8mmolC (gDCW)<SUP>−1</SUP> h<SUP>−1</SUP>) occur at late-exponential growth phase. Accordingly, extreme pathway analysis reduces the metabolic network into a macro reaction scheme, on which a dynamic metabolic model is built. The model is validated with experimental data, parameters are identified with confidence intervals, and global sensitivity analysis (Sobol׳ method) is performed. Model-based optimization predicts that ethanol productivity could increase from 34.2 in a typical batch process to 55.3mmolL<SUP>−1</SUP> h<SUP>−1</SUP> in an optimum fed-batch process with higher ethanol yield. Furthermore, the optimal operating regime was identified to be continuous fermentation process with gas stripping, in which a high ethanol productivity of 113mmolL<SUP>−1</SUP> h<SUP>−1</SUP>, <I>i.e.</I>, 26.8mmolC (gDCW)<SUP>−1</SUP> h<SUP>−1</SUP>, corresponding to 90.2% of the maximum theoretical ethanol yield could be achieved.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Metabolic flux distributions are visualized by dynamic metabolic flux analysis. </LI> <LI> Extreme pathway analysis reduces the network into a five-macro-reaction scheme. </LI> <LI> A dynamic model is established according to the scheme. </LI> <LI> The model is validated and global sensitivity analysis is performed. </LI> <LI> Model predicts chemostat offers both higher ethanol productivity and higher yield. </LI> </UL> </P>