Overexpression of a cytosolic hydroxymethylglutaryl-CoA reductase leads to squalene accumulation in yeast.
The enzyme 3-hydroxy-3-methylglutaryl-co-enzyme-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.
Polakowski
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T
Technische Universität Berlin, Institut für Biotechnologie, Fachgebiet Mikrobiologie und Genetik, Germany.
Stahl
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U
Lang
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C
D003600:Cytosol / Q000201:enzymology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013261:Sterols / Q000096:biosynthesis; D014158:Transcription, Genetic
D013261:Sterols; D006903:Hydroxymethylglutaryl CoA Reductases