Kinetic modeling to optimize pentose fermentation in Zymomonas mobilis
Article first published online: 28 MAR 2006
Copyright © 2006 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 94, Issue 2, pages 273–295, 5 June 2006
How to Cite
Altintas, M. M., Eddy, C. K., Zhang, M., McMillan, J. D. and Kompala, D. S. (2006), Kinetic modeling to optimize pentose fermentation in Zymomonas mobilis. Biotechnol. Bioeng., 94: 273–295. doi: 10.1002/bit.20843
- Issue published online: 24 APR 2006
- Article first published online: 28 MAR 2006
- Manuscript Accepted: 14 DEC 2005
- Manuscript Received: 15 MAR 2005
- Zymomonas mobilis;
- glucose and xylose metabolism;
- kinetic modeling;
- pentose phosphate pathway
Zymomonas mobilis engineered to express four heterologous enzymes required for xylose utilization ferments xylose along with glucose. A network of pentose phosphate (PP) pathway enzymatic reactions interacting with the native glycolytic Entner Doudoroff (ED) pathway has been hypothesized. We have investigated this putative reaction network by developing a kinetic model incorporating all of the enzymatic reactions of the PP and ED pathways, including those catalyzed by the heterologous enzymes. Starting with the experimental literature on in vitro characterization of each enzymatic reaction, we have developed a kinetic model to enable dynamic simulation of intracellular metabolite concentrations along the network of interacting PP and ED metabolic pathways. This kinetic model is useful for performing in silico simulations to predict how varying the different enzyme concentrations will affect intracellular metabolite concentrations and ethanol production rate during continuous fermentation of glucose and xylose mixtures. Among the five enzymes whose concentrations were varied as inputs to the model, ethanol production in the continuous fermentor was optimized when xylose isomerase (XI) was present at the highest level, followed by transaldolase (TAL). Predictions of the model that the interconnecting enzyme phosphoglucose isomerase (PGI) does not need to be overexpressed were recently confirmed through experimental investigations. Through such systematic analysis, we can develop efficient strategies for maximizing the fermentation of both glucose and xylose, while minimizing the expression of heterologous enzymes. © 2006 Wiley Periodicals, Inc.