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AssigneeCodexis, Inc.
InventorsEmily Mundorff, Erik De Vries
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The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme including the capability of reducing 5-((4S)-2-oxo-4-phenyl(1,3-oxazolidin-3-yl))-1-(4-fluorophenyl)pentane-1,5-dione to (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one. 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 the intermediate (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one in a process for making Ezetimibe.
A recombinant ketoreductase polypeptide capable of converting the substrate 5-((4S)-2-oxo-4-phenyl(1,3-oxazolidin-3-yl))-1-(4-fluorophenyl)pentane-1,5-dione to the product (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one at a rate that is improved over a reference polypeptide having the amino acid sequence of SEQ ID NO:
A recombinant ketoreductase polypeptide comprising a region with an amino acid sequence having at least about 85% identity to residues 90 to 211 of a reference sequence of SEQ ID NO:128, 130 or 160, with the proviso that the ketoreductase polypeptide has at the residue corresponding to X145 a serine and at the residue corresponding to residue X190 a cysteine.
Dependencies are inferred from the claim text.