Ketoreductases for the production of (S,E)-methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-hroxypropyl)benzoate

  • US 8,088,610 B2
  • Filed: 09/29/2008
  • Issued: 01/03/2012
  • Est. Priority Date: 09/28/2007
  • Status: Active Grant
First Claim
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1. A recombinant or isolated ketoreductase polypeptide capable of converting the substrate 2-[3-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-oxopropyl]benzoic acid methyl ester to the product (S,E)-methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-hydroxypropyl)benzoate at a rate that is at least 1.5 times the rate of the polypeptide of SEQ ID NO:

  • 4, which comprises an amino acid sequence that is at least 90% identical to a reference sequence based on SEQ ID NO;

    2, 4 or 114 having the following features;

    residue corresponding to Y190 is proline;

    residue corresponding to L195 is arginine; and

    the residue corresponding to A202 in SEQ ID NO;

    2 or L202 in SEQ ID NO;

    4 or 114 is a tryptophan.

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