Abstract: The present disclosure provides engineered proline hydroxylase polypeptides for the production of hydroxylated compounds, polynucleotides encoding the engineered proline hydroxylases, host cells capable of expressing the engineered proline hydroxylases, and methods of using the engineered proline hydroxylases to prepare compounds useful in the production of active pharmaceutical agents.
Type:
Grant
Filed:
June 26, 2020
Date of Patent:
May 4, 2021
Assignee:
Codexis, Inc.
Inventors:
Haibin Chen, Yong Koy Bong, Fabien L. Cabirol, Anupam Gohel Prafulchandra, Tao Li, Jeffrey C. Moore, Martina Quintanar-Audelo, Yang Hong, Steven J. Collier, Derek Smith
Abstract: The disclosure relates to engineered enone reductase polypeptides having improved properties, polynucleotides encoding the engineered polypeptides, related vectors, host cells, and methods for making the engineered enone reductase polypeptides. The disclosure also provides methods of using the engineered enone reductase polypeptides for chemical transformations.
Type:
Grant
Filed:
October 17, 2019
Date of Patent:
May 4, 2021
Assignee:
Codexis, Inc.
Inventors:
Christopher K. Savile, Vesna Mitchell, Xiyun Zhang, Gjalt W. Huisman
Abstract: The present invention provides engineered phenylalanine ammonia lyase (PAL) polypeptides and compositions thereof, as well as polynucleotides encoding the engineered phenylalanine ammonia lyase (PAL) polypeptides. In some embodiments, the engineered PAL polypeptides are optimized to provide enhanced catalytic activity, as well as reduced sensitivity to proteolysis and increased tolerance to storage at elevated temperatures. In some embodiments, the engineered PAL polypeptides contain fewer phenylalanine residues than wild-type PAL polypeptides. The present invention also provides methods for the use of the compositions comprising the engineered PAL polypeptides for therapeutic and industrial purposes.
Type:
Grant
Filed:
February 12, 2018
Date of Patent:
May 4, 2021
Assignee:
Codexis, Inc.
Inventors:
Chinping Chng, William Casey Hallows, Nicholas J. Agard, Oscar Alvizo, Nikki Dellas, Gjalt W. Huisman, John Joseph Nicols
Abstract: The present disclosure relates to non-naturally occurring polypeptides useful for preparing Ezetimibe, polynucleotides encoding the polypeptides, and methods of using the polypeptides.
Type:
Grant
Filed:
December 12, 2019
Date of Patent:
May 4, 2021
Assignee:
Codexis, Inc.
Inventors:
Michael A. Crowe, Oscar Alvizo, Behnaz Behrouzian, Yong Koy Bong, Steven J. Collier, Anupam Gohel, Jagadeesh Mavinahalli, Naga K. Modukuru, Emily Mundorff, Derek J. Smith, Shiwei Song, Wan Lin Yeo
Abstract: The present disclosure provides engineered transaminase enzymes having improved properties as compared to a naturally occurring wild-type transaminase enzyme. Also provided are polynucleotides encoding the engineered transaminase enzymes, host cells capable of expressing the engineered transaminase enzymes, and methods of using the engineered transaminase enzymes to synthesize a variety of chiral compounds.
Type:
Grant
Filed:
December 17, 2019
Date of Patent:
May 4, 2021
Assignee:
Codexis, Inc.
Inventors:
Ish K. Dhawan, Gregory Miller, Xiyun Zhang
Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme including the capability of reducing 5-((4S)-2-oxo-4-phenyl (1,3-oxazolidin-3-yl))-1-(4-fluorophenyl) pentane-1,5-dione to (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one. 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 the intermediate (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one in a process for making Ezetimibe.
Abstract: The present invention provides improved P450-BM3 variants with improved activity. In some embodiments, the P450-BM3 variants exhibit improved activity over a wide range of substrates.
Type:
Grant
Filed:
June 2, 2020
Date of Patent:
April 20, 2021
Assignee:
Codexis, Inc.
Inventors:
Robert Osborne, Vesna Mitchell, Khin Yu Naing Htwe, Xiyun Zhang, Erika M. Milczek, Jeffrey C. Moore
Abstract: Provided herein are compositions, foods comprising nepenthesin or a derivative thereof and methods of using nepenthesin or a derivative thereof for modulating gluten intolerance and related conditions, such as celiac disease. Further provided herein are pharmaceutical compositions comprising nepenthesin or a derivative thereof and methods of using nepenthesin or a derivative thereof to treat bacterial infections of the gastrointestinal tract, such as C. difficile or H. pylori. Further provided herein are compositions comprising recombinant nepenthesin I or nepenthesin II, or homologous proteins, and methods for making the same.
Type:
Grant
Filed:
March 18, 2019
Date of Patent:
April 20, 2021
Assignee:
Codexis, Inc.
Inventors:
David C. Schriemer, Petr Man, Hynek Mrazek, Martial Rey
Abstract: The present invention provides engineered human alpha-galactosidase polypeptides and compositions thereof. The engineered human alpha-galactosidase polypeptides have been optimized to provide improved stability under both acidic (pH<4.5) and basic (pH>7) conditions. The invention also relates to the use of the compositions comprising the engineered human alpha-galactosidase polypeptides for therapeutic purposes.
Type:
Grant
Filed:
August 5, 2020
Date of Patent:
April 13, 2021
Assignee:
Codexis, Inc.
Inventors:
Nicholas J. Agard, Mathew G. Miller, Xiyun Zhang, Gjalt W. Huisman
Abstract: The present invention provides engineered phenylalanine ammonia-lyase (PAL) polypeptides and compositions thereof, as well as polynucleotides encoding the engineered phenylalanine ammonia-lyase (PAL) polypeptides.
Type:
Grant
Filed:
March 9, 2020
Date of Patent:
April 13, 2021
Assignee:
Codexis, Inc.
Inventors:
Gjalt W. Huisman, Nicholas J. Agard, Benjamin Mijts, Jonathan Vroom, Xiyun Zhang
Abstract: The present invention relates to non-naturally occurring polypeptides useful for preparing armodafinil, polynucleotides encoding the polypeptides, and methods of using the polypeptides. The non-naturally occurring polypeptides of the present invention are effective in carrying out biocatalytic conversion of the (i) 2-(benzhydrylsulfinyl)acetamide to (?)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide (armodafinil), or (ii) benzhydryl-thioacetic acid to (R)-2-(benzhydrylsulfinyl)acetic acid, which is a pivotal intermediate in the synthesis of armodafinil, in enantiomeric excess.
Type:
Grant
Filed:
August 17, 2020
Date of Patent:
March 30, 2021
Assignee:
Codexis, Inc.
Inventors:
Ee Lui Ang, Oscar Alvizo, Behnaz Behrouzian, Michael D. Clay, Steven J. Collier, Ellen D. Eberhard, Fu Fan, Shiwei Song, Derek J. Smith, Magnus Widegren, Robert Wilson, Junye Xu, Jun Zhu
Abstract: The invention described herein relates to methods and compositions for treatment of gluten intolerance and related conditions (e.g., celiac disease and gluten sensitivity), or inhibition of inflammation and/or immune response in the intestine due to antigenic food peptides, by administration of a pharmaceutical composition comprising one or more Nepenthes enzymes.
Abstract: The present disclosure provides engineered polypeptides having imine reductase activity, polynucleotides encoding the engineered imine reductases, host cells capable of expressing the engineered imine reductases, and methods of using these engineered polypeptides with a range of ketone and amine substrate compounds to prepare secondary and tertiary amine product compounds.
Type:
Grant
Filed:
August 25, 2020
Date of Patent:
March 16, 2021
Assignee:
Codexis, Inc.
Inventors:
Haibin Chen, Steven J. Collier, Jovana Nazor, Joly Sukumaran, Derek Smith, Jeffrey C. Moore, Gregory Hughes, Jacob Janey, Gjalt W. Huisman, Scott J. Novick, Nicholas J. Agard, Oscar Alvizo, Gregory A. Cope, Wan Lin Yeo, Stefanie Ng Minor
Abstract: The present invention provides engineered phenylalanine ammonia-lyase (PAL) polypeptides and compositions thereof, as well as polynucleotides encoding the engineered phenylalanine ammonia-lyase (PAL) polypeptides.
Type:
Grant
Filed:
October 15, 2019
Date of Patent:
March 9, 2021
Assignee:
Codexis, Inc.
Inventors:
Gjalt W. Huisman, Nicholas J. Agard, Benjamin Mijts, Jonathan Vroom, Xiyun Zhang
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.
Type:
Grant
Filed:
January 22, 2019
Date of Patent:
February 23, 2021
Assignee:
Codexis, Inc.
Inventors:
Jack Liang, Stephane J. Jenne, Emily Mundorff, Charlene Ching, John M. Gruber, Anke Krebber, Gjalt W. Huisman
Abstract: The present invention provides engineered tyrosine ammonia-lyase (TAL) polypeptides and compositions thereof. In some embodiments, the engineered TAL polypeptides have been optimized to provide enhanced catalytic activity and enhanced acid stability, while reducing sensitivity to proteolysis and increasing tolerance to acidic pH levels. The invention also provides methods for utilization of the compositions comprising the engineered TAL polypeptides for therapeutic and industrial purposes.
Type:
Grant
Filed:
June 10, 2019
Date of Patent:
January 26, 2021
Assignee:
Codexis, Inc.
Inventors:
Gjalt W. Huisman, Joyce Liu, Nikki Dellas, Chinping Chng, William Casey Hallows
Abstract: The present invention provides engineered pantothenate kinase (PanK) enzymes, polypeptides having PanK activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing PanK enzymes are also provided. The present invention further provides compositions comprising the PanK enzymes and methods of using the engineered PanK enzymes. The present invention finds particular use in the production of pharmaceutical compounds.
Type:
Grant
Filed:
July 2, 2019
Date of Patent:
January 12, 2021
Assignee:
Codexis, Inc.
Inventors:
Margie Tabuga Borra-Garske, Oscar Alvizo, Lillian Jasmine Miller, Jesse B. Slaton, Aksiniya Lyubenova Petkova, Nandhitha Subramanian, Joshua Kolev, Anna Fryszkowska, Agustina Rodriguez-Granillo, Grant Murphy
Abstract: The present invention provides engineered phenylalanine ammonia-lyase (PAL) polypeptides and compositions thereof, as well as polynucleotides encoding the engineered phenylalanine ammonia-lyase (PAL) polypeptides.
Type:
Grant
Filed:
October 15, 2019
Date of Patent:
December 22, 2020
Assignee:
Codexis, Inc.
Inventors:
Gjalt W. Huisman, Nicholas J. Agard, Benjamin Mijts, Jonathan Vroom, Xiyun Zhang
Abstract: The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes.
Type:
Grant
Filed:
July 13, 2020
Date of Patent:
December 15, 2020
Assignee:
Codexis, Inc.
Inventors:
Oscar Alvizo, David Elgart, Robert Kevin Orr, James Nicholas Riggins, Anna Fryszkowska, Katrina W. Lexa, Xiang Yi, Da Duan, Courtney Dianne Moffett, Nikki Dellas, Vesna Mitchell