Heterologous expression of MlcE in Saccharomyces cerevisiae provides resistance to natural and semi-synthetic statins

Ana Ley, Hilde Cornelijne Coumou, Rasmus John Normand Frandsen

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    Abstract

    Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme in cholesterol biosynthesis. Their extensive use in treatment and prevention of cardiovascular diseases placed statins among the best selling drugs. Construction of Saccharomyces cerevisiae cell factory for the production of high concentrations of natural statins will require establishment of a non-destructive self-resistance mechanism to overcome the undesirable growth inhibition effects of statins. To establish active export of statins from yeast, and thereby detoxification, we integrated a putative efflux pump-encoding gene mlcE from the mevastatin-producing Penicillium citrinum into the S. cerevisiae genome. The resulting strain showed increased resistance to both natural statins (mevastatin and lovastatin) and semi-synthetic statin (simvastatin) when compared to the wild type strain. Expression of RFP-tagged mlcE showed that MlcE is localized to the yeast plasma and vacuolar membranes. We provide a possible engineering strategy for improvement of future yeast based production of natural and semi-synthetic statins.
    Original languageEnglish
    JournalMetabolic Engineering Communications
    Volume2
    Pages (from-to)117-123
    Number of pages7
    ISSN2214-0301
    DOIs
    Publication statusPublished - 2015

    Bibliographical note

    Publsihed under a Creative Commons license

    Keywords

    • Polyketide
    • Statins
    • Saccharomyces cerevisiae
    • Transport
    • Cell factory
    • Resistance

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