Granted Patent
B2
US 12,252,723 · App. 18/352,899 · Granted Mar 18, 2025
Ketoreductase polypeptides and polynucleotides
Inventors:
Jeffrey C. Moore (Westfield, NJ); Jack Liang (South San Francisco, CA); Jonathan Penfield (Truckee, CA); Jovana Nazor (Milpitas, CA); Nikki Dellas (San Carlos, CA); Vesna Mitchell (Santa Clara, CA); Da Duan (Newark, CA); Iman Farasat (Rahway, NJ); Agustina Rodriguez-Granillo (Rahway, NJ); Grant Murphy (Rahway, NJ); Nicholas Marshall (Rahway, NJ)
Assignee:
Codexis, Inc.
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Abstract
The present invention provides engineered ketoreductase and phosphite dehydrogenase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase and phosphite dehydrogenase enzymes, as well as polynucleotides encoding the engineered ketoreductase and phosphite dehydrogenase enzymes, host cells capable of expressing the engineered ketoreductase and phosphite dehydrogenase enzymes, and methods of using the engineered ketoreductase and phosphite dehydrogenase enzymes to synthesize a chiral catalyst used in the synthesis of antiviral compounds, such as nucleoside inhibitors. The present invention further provides methods of using the engineered enzymes to deracemize a chiral alcohol in a one-pot, multi-enzyme system.
Claims (6)
1. An engineered phosphite dehydrogenase variant having at least 90% sequence identity to the polypeptide sequence SEQ ID NO: 172 wherein said engineered phosphite dehydrogenase variant comprises an alanine at position 44 as compared to SEQ ID NO: 172.
2. The engineered phosphite dehydrogenase variant of claim 1 , wherein said engineered phosphite dehydrogenase variant further comprises at least one substitution or substitution set as compared to SEQ ID NO: 172 at one or more positions selected from positions 10/73/78/137/323/325, 10/73/78/233/323, 10/73/137, 13/41/63/132/193/195, 18/119/124/132/137/145/158/175/177/293/317/323, 18/119/124/132/137/145/158/177/293/323, 18/119/124/132/137/145/293/323/334/336, 32/132/137/145/186/233/293/323/336, 41/88/193/195, 69/120/132/137/145/175/195/293/323, 113/132/145, 119/132/137/145/158/175/177/293/317/323, 132/135/136/137/145/293, 132/136/137/145/293, 132/137/145/233/308/323, 132/137/145/293/323, 132/145, 132/145/195/293/323, 137/233/303/323, and 266, wherein said positions are numbered with reference to SEQ ID NO: 172.
3. The engineered phosphite dehydrogenase variant of claim 1 , wherein said engineered phosphite dehydrogenase variant has at least 95% sequence identity to SEQ ID NO: 172.
4. The engineered phosphite dehydrogenase variant of claim 1 , wherein said engineered phosphite dehydrogenase variant comprises a substitution set as compared to SEQ ID NO: 172 as in any of the engineered phosphite dehydrogenase variants selected from SEQ ID NOS: 182, 186, 194, 196, 198, 198, 200, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 235, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, and 260.
5. The engineered phosphite dehydrogenase variant of claim 1 , wherein said engineered phosphite dehydrogenase variant comprises a polypeptide sequence selected from the sequences set forth in SEQ ID NOS: 182, 186, 194, 196, 198, 198, 200, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 235, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, and 260.
6. A composition comprising at least one phosphite dehydrogenase variant set forth in claim 1 .
Assignments (4)
SECURITY INTEREST
Recorded Feb 15, 2024
From: CODEXIS, INC.
To: INNOVATUS LIFE SCIENCES LENDING FUND I, LP, AS COLLATERAL AGENT
Reel/Frame 066600/0650 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 9, 2024
From: LIANG, JACK; NAZOR, JOVANA; DELLAS, NIKKI; MITCHELL, VESNA; DUAN, DA; PENFIELD, JONATHAN
To: CODEXIS, INC.
Reel/Frame 066431/0705 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 9, 2024
From: MOORE, JEFFREY C.; FARASAT, IMAN; RODRIGUEZ-GRANILLO, AGUSTINA; MURPHY, GRANT; MARSHALL, NICHOLAS
To: MERCK SHARP & DOHME CORP.
Reel/Frame 066550/0501 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 8, 2024
From: LIANG, JACK; NAZOR, JOVANA; PENFIELD, JONATHAN; DELLAS, NIKKI; MITCHELL, VESNA; DUAN, DA; MERCK SHARPE & DOHME CORP.
To: CODEXIS, INC.
Reel/Frame 066417/0205 →
Continuity (4)
Division
16605576
Provisional Application
62491161
· Apr 27, 2017
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