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Please use this identifier to cite or link to this item: http://hdl.handle.net/10204/4921

Title: Decision making in the development of a biocatalytic route for resolution of S-naproxen: from screening to scale-up
Authors: Steenkamp, LH
Brady, D
Keywords: Naproxen
Enantioselective catalysis
Bioprocess engineering
Enantiomeric ratio
Enantiomeric excess
Applied microbiology
Microbial biotechnology
Issue Date: Jun-2010
Publisher: Formatex Publishers
Citation: Steenkamp, LH and Brady, D. 2010. Decision making in the development of a biocatalytic route for resolution of S-naproxen: from screening to scale-up. Current research, Technology and Education Topics in Applied Microbiology and Microbial Biotechnology, Vol. 2(13) pp 980-987
Series/Report no.: Workflow;4480
Abstract: The non-steroidal anti-inflammatory drug naproxen is most effective as the single S-naproxen enantiomer. However, typical synthetic routes to naproxen yield the racemate of both the R and the S stereoisomers. Biocatalysts can be used to resolve racemic mixtures of naproxen esters using esterases or lipases. During research and development of this process we reached several decision points based on biocatalyst selection, reaction engineering, and process definition. These included reaction type (hydrolytic versus esterification options), substrate selection, biocatalyst selection, and reaction conditions. The study began with identification of a suitable lipase or esterase for biocatalytic enantiomeric resolution of R,S-naproxen to yield the single enantiomer S-naproxen with an enantiomeric ratio (E) in excess of 200. Approximately 650 unidentified fungi, yeasts and bacteria from culture collections were screened and more than 80 commercially available esterases and lipases. From this 9 enzymes were chosen to optimise using statistically designed experiments to find the most important factors which influenced the conversion and enantioselectivity. During the process development, decisions were made regarding hydrolytic versus esterification options, enzyme type, substrate size, co-solvent, and physical parameters. Final considerations were the optimised conversion and enantiomeric excess, reaction productivity, and enzyme cost to give a process which would be feasible on large scale. The result was a commercially viable reaction yielding an E of approximately 500 and enantiomeric excess of 99%. The decisions behind the selection of the route are broadly applicable to other biocatalytic processes.
Description: Copyright: 2010 Formatex.
URI: http://www.formatex.info/microbiology2/980-987.pdf
ISSN: 9788461461950
Appears in Collections:Enzyme technologies
General science, engineering & technology

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