Steenkamp, Lucia HBrady, D2011-03-282011-03-282010-06Steenkamp, L.H. 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 980-9879788461461950http://www.formatex.info/microbiology2/980-987.pdfhttp://hdl.handle.net/10204/4921Copyright: 2010 Formatex.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.enNaproxenEnantioselective catalysisBioprocess engineeringS-naproxenEnantiomeric ratioEnantiomeric excessBiocatalysisApplied microbiologyMicrobial biotechnologyArticleSteenkamp, L. H., & Brady, D. (2010). Decision making in the development of a biocatalytic route for resolution of S-naproxen: from screening to scale-up. http://hdl.handle.net/10204/4921Steenkamp, Lucia H, and D Brady "Decision making in the development of a biocatalytic route for resolution of S-naproxen: from screening to scale-up." (2010) http://hdl.handle.net/10204/4921Steenkamp LH, Brady D. Decision making in the development of a biocatalytic route for resolution of S-naproxen: from screening to scale-up. 2010; http://hdl.handle.net/10204/4921.TY - Article AU - Steenkamp, Lucia H AU - Brady, D AB - 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. DA - 2010-06 DB - ResearchSpace DP - CSIR KW - Naproxen KW - Enantioselective catalysis KW - Bioprocess engineering KW - S-naproxen KW - Enantiomeric ratio KW - Enantiomeric excess KW - Biocatalysis KW - Applied microbiology KW - Microbial biotechnology LK - https://researchspace.csir.co.za PY - 2010 SM - 9788461461950 T1 - Decision making in the development of a biocatalytic route for resolution of S-naproxen: from screening to scale-up TI - Decision making in the development of a biocatalytic route for resolution of S-naproxen: from screening to scale-up UR - http://hdl.handle.net/10204/4921 ER -