Ketoreductase polypeptides for the production of (S,E)-methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-hydroxypropyl)benzoate
AssigneeCodexis, Inc.
InventorsJack Liang, Birthe Borup, Vesna Mitchell, Emily Mundorff, James Lalonde, Gjalt Huisman
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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.
Claims14
A method for reducing the substrate 2-[3-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-oxopropyl]benzoic acid methyl ester of formula (I)
- to the product (S,E)-methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-hydroxypropyl)benzoate of formula (II),
- or for reducing the substrate 2-[2-[3-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-oxopropyl]phenyl]-2-propanol of formula (III)
- to the product (S,E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-(2-(2-hydroxypropan-2-yl)phenyl)propan-1-ol of formula (IV),
- which comprises contacting the substrate of formula (I) with a ketoreductase polypeptide 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 and having at position 190 a proline, at position 195 an arginine, and at position 202 a tryptophan, under reaction conditions suitable for reducing or converting the substrate to the product of formula (II).
A method for the synthesis of compound (V)
- or salts, hydrates or solvates thereof, wherein the method comprises:
- (a) a step of reducing the substrate 2-[3-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-oxopropyl]benzoic acid methyl ester of formula (I)
- to the product (S,E)-methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-hydroxypropyl)benzoate of formula (II)
- or (b) a step of reducing substrate 2-[2-[3-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-oxopropyl]phenyl]-2-propanol of formula (III)
- to the product (S,E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-(2-(2-hydroxypropan-2-yl)phenyl)propan-1-ol of formula (IV)
- by contacting the substrate of formula (I) or formula (II) with the ketoreductase polypeptide 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 and having at position 190 a proline, at position 195 an arginine, and at position 202 a tryptophan, under reaction conditions suitable for reducing or converting the substrate to the product of formula (II).
Dependencies are inferred from the claim text.