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Metab Eng. 2006 Mar;8(2):102-11. Epub 2005 Nov 10.

In silico aided metabolic engineering of Saccharomyces cerevisiae for improved bioethanol production.

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Center for Microbial Biotechnology, BioCentrum-DTU, Building 223, Technical University of Denmark, DK-2800 Kgs, Lyngby, Denmark.


In silico genome-scale cell models are promising tools for accelerating the design of cells with improved and desired properties. We demonstrated this by using a genome-scale reconstructed metabolic network of Saccharomyces cerevisiae to score a number of strategies for metabolic engineering of the redox metabolism that will lead to decreased glycerol and increased ethanol yields on glucose under anaerobic conditions. The best-scored strategies were predicted to completely eliminate formation of glycerol and increase ethanol yield with 10%. We successfully pursued one of the best strategies by expressing a non-phosphorylating, NADP(+)-dependent glyceraldehyde-3-phosphate dehydrogenase in S. cerevisiae. The resulting strain had a 40% lower glycerol yield on glucose while the ethanol yield increased with 3% without affecting the maximum specific growth rate. Similarly, expression of GAPN in a strain harbouring xylose reductase and xylitol dehydrogenase led to an improvement in ethanol yield by up to 25% on xylose/glucose mixtures.

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