Polypeptides for a ketoreductase-mediated stereoselective route to alpha chloroalcohols
AssigneeCodexis, Inc.
InventorsYong Koy Bong, Michael Vogel, Steven J. Collier, Vesna Mitchell, Jagadeesh Mavinahalli
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Abstract
The present disclosure relates to engineered ketoreductase polypeptides and uses thereof for the preparation of α chloroalcohols from α chloroketones. Also provided are polynucleotides encoding the engineered ketoreductase polypeptides and host cells capable of expressing the engineered ketoreductase polypeptides.
Claims22
An engineered ketoreductase polypeptide capable of converting (S)-tert-butyl 4-chloro-3-oxo-1-phenylbutan-2-ylcarbamate to tert-butyl (2S,3R)-4-chloro-3-hydroxy-1-phenylbutan-2-ylcarbamate with a relative activity at least 1.2-fold that of the polypeptide of SEQ ID NO:2, wherein the engineered ketoreductase polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO:2 and includes one or more amino acid substitutions relative to SEQ ID NO:
- 2, selected from the group consisting of P2L;
- V28A;
- A34S;
- A47V;
- E50K;
- D81N;
- 590V;
- I191L;
- I91W;
- I91R;
- I91K;
- K94R;
- D112Y;
- G117D;
- S143R;
- V144T;
- G145A;
- R148H;
- A150G;
- F152L;
- N153G;
- N153V;
- N153H;
- T1585;
- G190A;
- S198N;
- I199M;
- I199L;
- I199N;
- M200I;
- A217T;
- I225V;
- P231F;
- A232V;
- E233Q;
- D244G;
- F260Y;
- and S261N.
Dependencies are inferred from the claim text.