Wednesday, July 29, 2009 - 10:30 AM
S112
From “Enzyme” to “Catalyst” – Technology Development and Commercial Applications
Scott Novick and Gjalt Huisman. Codexis Inc.,, 200 Penobscot Drive, Redwood City, CA 94063
Directed evolution strategies, which include generation of mutants and screening for improved function, provide the means to develop novel and superior biocatalysts that fit the desired chemical processes. Protein Sequence Activity Relationship (ProSAR) exploits the information contained in the sequence-activity data to enable a mutation-oriented approach to enzyme optimization. Combined with recursive DNA shuffling, this method proved to be substantially more efficient and less blind than traditional hit-oriented approaches. A new tool, CodexTM biocatalyst panels, can further accelerate development of commercially viable biocatalysts for a variety of chemical syntheses.
A CodexTM biocatalyst panel is a set of enzyme variants that are designed to accept a wide range of substrates, produce different stereoisomers with high selectivity, be chemically robust, and be manufactured at commercial scale. The plate variants are also designed to yield structure-function information that can be used to provide a jumpstart to evolution. To achieve these goals, a development strategy was conceived consisting of four steps: evolve a robust enzyme variant, generate binding pocket diversity, screen on multiple diverse substrates, and select variants with broad phenotypic diversity. This strategy was then used to produce five Codex™ Panels: ketoreductase, transaminase, ene reductase, acylase, and halohydrin dehalogenase. This strategy and the development of the panels will be presented. In addition, examples of the deployment of evolved biocatalyst using panels, shuffling and ProSAR in the manufacturing of advanced intermediates and active pharmaceutical ingredients itself will be presented, including instances where there are no chemical equivalents to the enzymatic reaction.
A CodexTM biocatalyst panel is a set of enzyme variants that are designed to accept a wide range of substrates, produce different stereoisomers with high selectivity, be chemically robust, and be manufactured at commercial scale. The plate variants are also designed to yield structure-function information that can be used to provide a jumpstart to evolution. To achieve these goals, a development strategy was conceived consisting of four steps: evolve a robust enzyme variant, generate binding pocket diversity, screen on multiple diverse substrates, and select variants with broad phenotypic diversity. This strategy was then used to produce five Codex™ Panels: ketoreductase, transaminase, ene reductase, acylase, and halohydrin dehalogenase. This strategy and the development of the panels will be presented. In addition, examples of the deployment of evolved biocatalyst using panels, shuffling and ProSAR in the manufacturing of advanced intermediates and active pharmaceutical ingredients itself will be presented, including instances where there are no chemical equivalents to the enzymatic reaction.
See more of Advances in biocatalyst development (emphasis on novel biocatalysts)
See more of Invited Oral Papers
See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)
See more of Invited Oral Papers
See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)