Ketoreductases and uses thereof
AssigneeCodexis, Inc.
InventorsCharlene Ching, John M. Gruber, Gjalt W. Huisman, Emily Mundorff, Lisa M. Newman
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Abstract
The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds.
Claims24
A recombinant ketoreductase polypeptide capable of converting the compound 1-[4-(4-fluoro2-methyl-1H-indol-5-yloxy)-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-propan-2-one to 1-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-propan-2-ol, with at least 1.5 times the activity of the polypeptide of SEQ ID NO:2, the polypeptide comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO:2 or SEQ ID NO:4 and having (a) an aromatic amino acid or G at the amino acid residue corresponding to residue 94 of SEQ ID NO:2 or SEQ ID NO:4, or (b) an amino acid other than S and N at the amino acid residue corresponding to residue 96 of SEQ ID NO:2 or SEQ ID NO:4.
Dependencies are inferred from the claim text.