• Open Access

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

Authors

  • Bart Oud,

    1. Department of Biotechnology, Delft University of Technology and Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands
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  • Antonius J. A. van Maris,

    1. Department of Biotechnology, Delft University of Technology and Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands
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  • Jean-Marc Daran,

    1. Department of Biotechnology, Delft University of Technology and Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands
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  • Jack T. Pronk

    1. Department of Biotechnology, Delft University of Technology and Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands
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Correspondence: Jack Pronk, Department of Biotechnology, Delft University of Technology and Kluyver Centre for Genomics of Industrial Fermentation, Julianalaan 67, 2628 BC Delft, The Netherlands. Tel.: +31 152782416; fax: +31 152782355; e-mail j.t.pronk@tudelft.nl

Abstract

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages.

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