Kinetic Modeling to Optimize Pentose Fermentation in Zymomonas mobilis

Mehmet M. Altintas, Christina K. Eddy, Min Zhang, James D. McMillan, Dhinakar S. Kompala

Research output: Contribution to journalArticlepeer-review

46 Scopus Citations

Abstract

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.

Original languageAmerican English
Pages (from-to)273-295
Number of pages23
JournalBiotechnology and Bioengineering
Volume94
Issue number2
DOIs
StatePublished - 2006

NREL Publication Number

  • NREL/JA-510-37326

Keywords

  • Glucose and xylose metabolism
  • Kinetic modeling
  • Pentose phosphate pathway
  • Zymomonas mobilis

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