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Isoprenoid compounds

  • US 8,609,371 B2
  • Filed: 08/12/2009
  • Issued: 12/17/2013
  • Est. Priority Date: 08/12/2008
  • Status: Active Grant
First Claim
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1. A nucleic acid molecule that encodes a variant squalene synthase enzyme, wherein the variant enzyme comprises one or more amino acid substitutions in the squalene synthase enzyme whose sequence is set forth in SEQ ID NO:

  • 4, and comprises a sequence of amino acid residues that is at least 95% identical to the squalene synthase enzyme whose sequence is set forth in SEQ ID NO;

    4, whereby;

    the variant enzyme exhibits reduced cellular squalene synthase activity compared to the enzyme that does not comprise the one or more amino acid substitution(s);

    the variant enzyme, when present and expressed in vivo in a eukaryotic microbial host as the only squalene synthase species, catalyzes the synthesis of squalene at a sufficiently high rate that supplementation of the eukaryotic microbial host with a sterol is not required for growth; and

    the eukaryotic microbial host produces a terpene product in medium lacking a sterol.

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