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:
April 6, 2021
Date of Patent:
January 3, 2023
Assignee:
Codexis, Inc.
Inventors:
Ish K. Dhawan, Gregory Miller, Xiyun Zhang
Abstract: Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided.
Type:
Grant
Filed:
May 15, 2020
Date of Patent:
December 27, 2022
Assignee:
Codexis, Inc.
Inventors:
Xiyun Zhang, Russell Javiniar Sarmiento, Donald Scott Baskerville, Gjalt W. Huisman
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. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N-methyl-3-keto-3-(2-thienyl)-1-propanamine to (S)—N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.
Type:
Grant
Filed:
July 17, 2020
Date of Patent:
November 29, 2022
Assignee:
Codexis, Inc.
Inventors:
Christopher Savile, John M. Gruber, Emily Mundorff, Gjalt W. Huisman, Steven J. Collier
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:
November 15, 2022
Assignee:
Codexis, Inc.
Inventors:
Nicholas J. Agard, Mathew G. Miller, Xiyun Zhang, Gjalt W. Huisman
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 14, 2021
Date of Patent:
October 25, 2022
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 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.
Abstract: The present invention provides engineered galactose oxidase (GOase) enzymes, polypeptides having GOase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing GOase enzymes are also provided. The present invention further provides compositions comprising the GOase enzymes and methods of using the engineered GOase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds.
Type:
Grant
Filed:
July 2, 2019
Date of Patent:
October 11, 2022
Assignee:
Codexis, Inc.
Inventors:
Christopher Michael Micklitsch, Oscar Alvizo, Jovana Nazor, Harvinder Chagger Maniar, Mikayla Jianghongxia Krawczyk, Margie Tabuga Borra-Garske, Nandhitha Subramanian, Anna Fryszkowska, Nicholas M. Marshall, Agustina Rodriguez-Granillo, Deeptak Verma, Dewan Andrews
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 chiral compounds.
Type:
Grant
Filed:
October 26, 2020
Date of Patent:
August 30, 2022
Assignee:
Codexis, Inc.
Inventors:
Jack S Liang, Stephan Jenne, Emily Mundorff, Rama Voladri, James J. Lalonde, Gjalt W. Huisman
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 thermostability, serum stability, improved cellular uptake, stability under both acidic (pH<4) and basic (pH>7) conditions, reduced immunogenicity, and improved globotriaosylceramide removal from cells. The invention also relates to the use of the compositions comprising the engineered human alpha-galactosidase polypeptides for therapeutic purposes.
Type:
Grant
Filed:
December 19, 2019
Date of Patent:
August 30, 2022
Assignee:
Codexis, Inc.
Inventors:
William Casey Hallows, Kristen Jean Vallieu, Nikki Dellas, Yu Zhu, Judy Victoria Antonio Viduya, Chinping Chng, Antoinette Sero, Gjalt W. Huisman, Rachel Cathleen Botham, Moulay Hicham Alaoui Ismaili
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:
January 14, 2021
Date of Patent:
August 23, 2022
Assignee:
Codexis, Inc.
Inventors:
Gjalt W. Huisman, Joyce Liu, Nikki Dellas, Chinping Chng, William Casey Hallows
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 26, 2020
Date of Patent:
August 2, 2022
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:
February 24, 2021
Date of Patent:
July 12, 2022
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 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:
November 6, 2020
Date of Patent:
July 5, 2022
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 transaminase polypeptides useful for the synthesis of chiral amine compounds under industrially relevant conditions. The invention also provides polynucleotides encoding the engineered transaminase polypeptides, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases for the production of chiral amine compounds.
Type:
Grant
Filed:
May 23, 2018
Date of Patent:
June 14, 2022
Assignee:
Codexis, Inc.
Inventors:
Scott J. Novick, Nikki Dellas, Oscar Alvizo, Ravi David Garcia, Charlene Ching, David Entwistle
Abstract: The present application 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:
September 2, 2020
Date of Patent:
June 7, 2022
Assignee:
Codexis, Inc.
Inventors:
Oscar Alvizo, Melissa Ann Mayo, Jeffrey C. Moore
Abstract: Disclosed are methods for building a sequence activity model with reference to structural data, which model can be used to guide directed evolution of proteins having beneficial properties. Some embodiments use genetic algorithms and structural data to filter out uninformative data. Some embodiments use a support vector machine to train the sequence activity model. The filtering and training methods can generate a sequence activity model having higher predictive power than conventional modeling methods. Systems and computer program products implementing the methods are also provided.
Type:
Grant
Filed:
June 6, 2019
Date of Patent:
May 24, 2022
Assignee:
Codexis, Inc.
Inventors:
Russell Javiniar Sarmiento, Donald Scott Baskerville, Xiyun Zhang
Abstract: The present invention provides engineered transglutamirase enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, methods of producing these enzymes, and methods of using the engineered transglutaminase enzymes.
Type:
Grant
Filed:
November 2, 2018
Date of Patent:
May 3, 2022
Assignee:
Codexis, Inc.
Inventors:
Jovana Nazor, Jie Yang, Goutami Banerjee, Xiyun Zhang, James Nicholas Riggins, Erika M. Milczek, Jeffrey C. Moore
Abstract: The present invention provides engineered ?-glucosidase (BGL) enzymes, polypeptides having BGL activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. The present invention also provides compositions comprising the enzymes, and methods of using the engineered BGL enzymes to make products with ?-glucose linkages.
Type:
Grant
Filed:
June 9, 2017
Date of Patent:
April 12, 2022
Assignee:
Codexis, Inc.
Inventors:
Jack Liang, Jonathan Vroom, Stephanie Sue Galanie, Nikki Dellas, Ravi David Garcia