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Overexpression of O-methyltransferase leads to improved vanillin production in baker's yeast only when complemented with model-guided network engineering

Authors

  • Ana Rita Brochado,

    1. Department of Systems Biology, Center for Microbial Biotechnology, Technical University of Denmark, Lyngby, Denmark
    2. European Molecular Biology Laboratory, Structural and Computational Biology Unit, EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany; telephone: +49-6221-387-8473; fax: +49-6221-387-8517
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  • Kiran R. Patil

    Corresponding author
    1. European Molecular Biology Laboratory, Structural and Computational Biology Unit, EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany; telephone: +49-6221-387-8473; fax: +49-6221-387-8517
    • European Molecular Biology Laboratory, Structural and Computational Biology Unit, EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany; telephone: +49-6221-387-8473; fax: +49-6221-387-8517.
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  • Author's contribution: ARB and KRP conceived the study. ARB designed and carried out the experiments. ARB and KRP analyzed the results and wrote the manuscript.

Abstract

Overproduction of a desired metabolite is often achieved via manipulation of the pathway directly leading to the product or through engineering of distant nodes within the metabolic network. Empirical examples illustrating the combined effect of these local and global strategies have been so far limited in eukaryotic systems. In this study, we compared the effects of overexpressing a key gene in de novo vanillin biosynthesis (coding for O-methyltransferase, hsOMT) in two yeast strains, with and without model-guided global network modifications. Overexpression of hsOMT resulted in increased vanillin production only in the strain with model-guided modifications, exemplifying advantage of using a global strategy prior to local pathway manipulation. Biotechnol. Bioeng. 2013; 110: 656–659. © 2012 Wiley Periodicals, Inc.

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