4.3 Article

Evolutionary engineering of Saccharomyces cerevisiae for efficient aerobic xylose consumption

Journal

FEMS YEAST RESEARCH
Volume 12, Issue 5, Pages 582-597

Publisher

OXFORD UNIV PRESS
DOI: 10.1111/j.1567-1364.2012.00808.x

Keywords

directed evolution; metabolic engineering; xylose; Saccharomyces cerevisiae; transcriptomics

Funding

  1. Division of Bioprocess Research & Development, Merck Research Labs, Merck Co., Inc.
  2. Chalmers Foundation
  3. Knut and Alice Wallenberg Foundation

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Industrial biotechnology aims to develop robust microbial cell factories, such as Saccharomyces cerevisiae, to produce an array of added value chemicals presently dominated by petrochemical processes. Xylose is the second most abundant monosaccharide after glucose and the most prevalent pentose sugar found in lignocelluloses. Significant research efforts have focused on the metabolic engineering of S similar to cerevisiae for fast and efficient xylose utilization. This study aims to metabolically engineer S similar to cerevisiae, such that it can consume xylose as the exclusive substrate while maximizing carbon flux to biomass production. Such a platform may then be enhanced with complementary metabolic engineering strategies that couple biomass production with high value-added chemical. Saccharomyces cerevisiae, expressing xylose reductase, xylitol dehydrogenase and xylulose kinase, from the native xylose-metabolizing yeast Pichia stipitis, was constructed, followed by a directed evolution strategy to improve xylose utilization rates. The resulting S similar to cerevisiae strain was capable of rapid growth and fast xylose consumption producing only biomass and negligible amount of byproducts. Transcriptional profiling of this strain was employed to further elucidate the observed physiology confirms a strongly up-regulated glyoxylate pathway enabling respiratory metabolism. The resulting strain is a desirable platform for the industrial production of biomass-related products using xylose as a sole carbon source.

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