Two-stage transcriptional reprogramming in Saccharomyces cerevisiae for optimizing ethanol production from xylose

Metab Eng. 2014 Jul;24:150-9. doi: 10.1016/j.ymben.2014.05.001. Epub 2014 May 21.


Conversion of lignocellulosic material to ethanol is a major challenge in second generation bio-fuel production by yeast Saccharomyces cerevisiae. This report describes a novel strategy named "two-stage transcriptional reprogramming (TSTR)" in which key gene expression at both glucose and xylose fermentation phases is optimized in engineered S. cerevisiae. Through a combined genome-wide screening of stage-specific promoters and the balancing of the metabolic flux, ethanol yields and productivity from mixed sugars were significantly improved. In a medium containing 50g/L glucose and 50g/L xylose, the top-performing strain WXY12 rapidly consumed glucose within 12h and within 84h it consistently achieved an ethanol yield of 0.48g/g total sugar, which was 94% of the theoretical yield. WXY12 utilizes a KGD1 inducible promoter to drive xylose metabolism, resulting in much higher ethanol yield than a reference strain using a strong constitutive PGK1 promoter. These promising results validate the TSTR strategy by synthetically regulating the xylose assimilation pathway towards efficient xylose fermentation.

Keywords: Ethanol; Saccharomyces cerevisiae; Two-stage transcription reprogramming; Xylose; Xylose reductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ethanol / metabolism*
  • Gene Expression Regulation, Fungal / genetics*
  • Metabolic Engineering*
  • Promoter Regions, Genetic*
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Transcription, Genetic / genetics*
  • Xylose / metabolism*


  • Ethanol
  • Xylose