Polynucleotides encoding engineered ketoreductase polypeptides
AssigneeCodexis, Inc.
InventorsChristopher Savile, John M. Gruber, Emily Mundorff, Gjalt Huisman, Steven James Collier
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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. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N-methyl-3-keto-3-(2-thienyl)-1-propanamine to (S)—N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.
Claims9
An isolated or recombinant polynucleotide encoding a ketoreductase polypeptide, wherein the polypeptide has an amino acid sequence that is at least 90% identical to a reference sequence of SEQ ID NO:2 and has at least the following features:
- (a) the residue corresponding to residue X94 is aspartic acid, (b) the residue corresponding to residue X145 is phenylalanine;
- (c) the residue corresponding to residue X190 is proline, and (d) wherein the residue corresponding to X196 is a non-polar or aliphatic residue.
Dependencies are inferred from the claim text.