Overexpression of a cytosolic hydroxymethylglutaryl-CoA reductase leads to squalene accumulation in yeast |
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Authors: | T Polakowski U Stahl C Lang |
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Institution: | Technische Universit?t Berlin, Institut für Biotechnologie, Fachgebiet Mikrobiologie und Genetik, Gustav-Meyer-Allee 25, 13355 Berlin, Germany Tel.: +49 30 31472751 Fax: +49 30 31472922 e-mail: C.Lang@LB.TU-Berlin.de, DE
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Abstract: | The enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase is known as the rate-limiting enzyme in early sterol
biosynthesis in eukaryotic cells. To eliminate this regulation in the yeast Saccharomyces cerevisiae, a truncated HMG1 gene, producing a form of the enzyme that lacks the membrane-binding region (i.e. amino acids 1–552), was constructed and
overexpressed in this yeast. The transformed strains accumulated large amounts of the sterol precursor squalene, while the
levels of ergosterol and a number of other sterol compounds were only slightly elevated. These findings suggest that HMG-CoA
reductase is not the only rate-limiting step in sterol synthesis and its overexpression cannot significantly influence this
pathway beyond the sterol precursor squalene.
Received: 9 June 1997 / Received revision: 1 September 1997 / Accepted: 19 September 1997 |
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