Codexis, Inc.

Metabolix, Inc.

Pfizer Corporation

Crosswalk Therapeutics, Inc.

Maxygen, Inc.

Codexis Mayflower Holdings, LLC

Syntis Bio, Inc.

Maxygar, Inc.

Gjalt W Huisman

Emily Mundorff

Nicholas John Agard

Xiyun Zhang

John M Gruber

Steven James Collier

Oscar Alvizo

Jack S Liang

Christopher K Savile

Lisa Marie Newman

Jonathan Vroom

Stephane J Jenne

Benjamin Mijts

Derek J Smith

Jeffrey C Moore

Jovana Nazor

Jacob M Janey

Wan Lin Yeo

Joly Sukumaran

Haibin Chen

Scott J Novick

Gregory Hughes

Stefanie Ng Minor

Gregory Allan Cope

Vesna Mitchell

Charlene Ching

James Joseph LaLonde

Oliver P Peoples

Anke Krebber

S Christopher Davis

Chinping Chng

Rama Voladri

Mathew G Miller

Richard John Fox

Stephan Jenne

John H Grate

Frank Anthony Skraly

Nikki Dellas

William Casey Hallows

Willem P C Stemmer

Melissa Ann Mayo

James Nicholas Riggins

Xiang Yi

Jonathan S Penfield

Vesna Gavrilovic

Jeremy S Minshull

David P Martin

Phillip A Patten

Jon Edward Ness

Linda A Castle

Matthew B Tobin

Joseph A Affholter

David Elgart

Claus M Krebber

Venkiteswatan Mani Subramanian

Stephen DelCardayre

Yasushi Saotome

Ying-Xin Zhang

Ling Yuan

Jared Davis

Lorraine Joan Giver

Behnaz Behrouzian

Steven Henry Bass

Anthony Cox

Lara Madison

Roger Arthur Sheldon

Moulay Hicham Alaoui Ismaili

David R Gray

Steven K Ma

Li A Wang

Yu Zhu

Rachel Cathleen Botham

James LaLonde

Jian Ding

Robert Osborne

Birthe Borup

Joyce Liu

Donald Scott Baskerville

Kristen Jean Vallieu

Antoinette Sero

Russell Javiniar Sarmiento

Jed Lee Hubbs

Laura Z Luo

Jun Zhu

Sun Ai Raillard

Judy Victoria Antonio Viduya

Stephanie Sue Galanie

Simon Christopher Davis

Steve Bass

Kerryn McCluskie

Anke Kebber

Leann Quertinmont Teadt

Nikki D Kruse

Tony Cox

Venkitswaran Subramanian

John Joseph Nicols

Adam P Silverman

David William Homan

Kierra Aleece Franklin

Jessica P Lao

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.

Ketoreductase polypeptides for the production of (R)-3-hydroxythiolane

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.

Enone reductases

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.

Engineered ketoreductase polypeptides

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.

Human alpha-galactosidase variants

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.

The present invention provides engineered RNA polymerase variants and compositions comprising these variants. The present invention further provides engineered T7 RNA polymerase variants and compositions comprising these variants. These variants have been evolved for selective incorporation of the m7G(5')ppp(5′)m7G cap analog over GTP at the initiation of in vitro transcription. The present invention also provides methods for selective capping of RNA transcripts.

T7 RNA polymerase variants

The present invention provides engineered methionine gamma lyase polypeptides and compositions thereof. The engineered methionine gamma lyase polypeptides have been optimized to provide improved thermostability, protease stability, and stability under a range of pH conditions, including acidic (pH<7) conditions. The present invention also relates to the use of the compositions comprising the engineered methionine gamma lyase polypeptides for therapeutic purposes.

Engineered methionine gamma lyase variants

The present invention provides engineered acid alpha-glucosidase (GAA) polypeptides and compositions thereof. In some embodiments, the engineered GAA polypeptides have been optimized to provide increased expression, stability at neutral pH, and activity in cell lysates. The invention also provides methods for utilization of the compositions comprising the engineered GAA polypeptides for therapeutic and other purposes.

Engineered acid alpha-glucosidase variants

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.

Engineered phenylalanine ammonia lyase polypeptides

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.

Engineered imine reductases and methods for the reductive amination of ketone and amine compounds

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.

Automated screening of enzyme variants

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)&#x2014;N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

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&#x3c;4.5) and basic (pH&#x3e;7) conditions. The invention also relates to the use of the compositions comprising the engineered human alpha-galactosidase polypeptides for therapeutic purposes.

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Redwood City, CA, United States of America

Gjalt W Huisman