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MP10:Markwalter:Process Improvement of Biocatalytic Reaction Screening through Automation and Parallel Experimentation

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Process Improvement of Biocatalytic Reaction Screening through Automation and Parallel Experimentation
Chester Markwalter* (1), Steven Goldberg (2), Animesh Goswami (2), Erik Rubin (2), Vicky Vydra (2)

(1) Department of Chemical Engineering, University of Delaware

(2) Chemical Development, Bristol-Myers Squibb, New Brunswick, NJ


Biocatalysts enable the development of safe, efficient, and environmentally friendly chemical processes through highly selective transformations that may be otherwise impractical. Typically, biocatalyst selection for a desired transformation begins with screening a library of enzymes on the basis of product yield and/or selectivity. Commonly, the screening process is manual and labor intensive, which limits the number of experiments that can be conducted in parallel by a single scientist. The use of laboratory automation enables process improvements such as reduced material consumption, increased throughput, and improved data quality with the ability to limit experimental variability across a broad experimental space. For these reasons, an automated workflow for screening biocatalytic reactions was developed, the details of which are presented here. The first stage in developing the automated workflow involved the design of a flexible procedure for enzyme library assembly. This novel method allowed for plates customized for a desired transformation that accommodated both automated powder dispense and lyophilization techniques. In the second stage, an automated biocatalytic reaction workflow was developed and tested using model enzymatic ester hydrolysis and ketone reduction reactions, two common biocatalytic transformations employed in active pharmaceutical ingredient synthesis. Consistent and reproducible results from these trials established proof-of-concept for the workflow. Implementation of an automated workflow is expected to be highly impactful by increasing the productivity of scientists and expanding the screening space.



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SLAS2012 Posters(1 C)
The Market Place for Lab Automation & Screening  The Market Place