A dynamic flux balance model and bottleneck identification of glucose, xylose, xylulose co-fermentation in Saccharomyces cerevisiae

Bioresour Technol. 2015;188:153-60. doi: 10.1016/j.biortech.2015.02.015. Epub 2015 Feb 20.


A combination of batch fermentations and genome scale flux balance analysis were used to identify and quantify the rate limiting reactions in the xylulose transport and utilization pathway. Xylulose phosphorylation by xylulokinase was identified as limiting in wild type Saccharomyces cerevisiae, but transport became limiting when xylulokinase was upregulated. Further experiments showed xylulose transport through the HXT family of non-specific glucose transporters. A genome scale flux balance model was developed which included an improved variable sugar uptake constraint controlled by HXT expression. Model predictions closely matched experimental xylulose utilization rates suggesting the combination of transport and xylulokinase constraints is sufficient to explain xylulose utilization limitation in S. cerevisiae.

Keywords: Cellulosic ethanol; Fermentation; Flux balance analysis; Pentose; Xylose.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Cellulose / chemistry
  • Ethanol / chemistry
  • Fermentation
  • Genotype
  • Glucose / chemistry*
  • Industrial Microbiology
  • Monte Carlo Method
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Saccharomyces cerevisiae / metabolism*
  • Xylose / chemistry*
  • Xylulose / chemistry*


  • Ethanol
  • Xylulose
  • Adenosine Triphosphate
  • Cellulose
  • Xylose
  • Phosphotransferases (Alcohol Group Acceptor)
  • xylulokinase
  • Glucose