Ketoreductase polypeptides for the synthesis of chiral compounds
AssigneeCodexis, Inc.
InventorsOscar Alvizo, Nicholas J. Agard, Xinkai Xie, David Entwistle, Birgit Kosjek
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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.
Claims43
An engineered polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:2 and at least one substitution at a position selected from X68, X94, X102, X110, X114, X135, X144, X145, X147, X149, X150, X153, X158, X173, X175, X190, X196, X197, X198, X199, X201, X202, X203, X205, X206, X207, X209, X210, X211, X212, X213, X217, X233, X249, X250, and X252, and wherein said polypeptide has greater 2a:2c selectivity as compared to SEQ ID NO:2.
An engineered polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:4 and at least one substitution at a position selected from X94, X144, X145, X150, X190, and X249, and wherein said polypeptide has greater 2a:2c selectivity as compared to SEQ ID NO:4.
An engineered polypeptide comprising an amino acid sequence with at least 80% sequence identity to a reference sequence of SEQ ID NO:
- 10 and at least one substitution at a position selected from X145, X150, X153, X190, X198, X206, and X211, and wherein said polypeptide has greater 2a:2c selectivity as compared to SEQ ID NO:
- 10.
An engineered polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:26 and at least one substitution at a position selected from X94, X147, X153, X175, X190, X196, X199, X201, X202, X203, X206, X207, X209, X210, X211, X212, X213, X217, and wherein said polypeptide has greater 2a:2c selectivity as compared to SEQ ID NO:26.
An engineered polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:42 and at least one substitution at a position selected from X68, X94, X102, X110, X114, X135, X149, X150, X153, X158, X173, X190, X196, X197, X198, X203, X205, X207, X209, X212, X213, X217, X233, X249, X250, X252, and wherein said polypeptide has greater 2a:2c selectivity as compared to SEQ ID NO:42.
An engineered polypeptide having ketoreductase activity, wherein the polypeptide comprises SEQ ID NO:240.
An engineered polypeptide having ketoreductase activity, wherein the polypeptide comprises SEQ ID NO:239.
Dependencies are inferred from the claim text.