Reaction engineering of biocatalytic (S)-naproxen synthesis integrating in-line process monitoring by Raman spectroscopy

Journal
Reaction chemistry and engineering  
Volume
2
Issue
4
Start Page
531
End Page
540
Citation
Reaction Chemistry and Engineering 4 (2): 531-540 (2017-08-01)
Publisher DOI
10.1039/c7re00043j
Scopus ID
2-s2.0-85051327242
Publisher
Royal Society of Chemistry
Biocatalytic (S)-naproxen synthesis using an (S)-selective arylmalonate decarboxylase mutant (AMDase G74C/M159L/C188G/V43I/A125P/V156L, AMDase-CLGIPL) exposes a promising environmentally friendly alternative to conventional chemical synthesis strategies. The reaction progress of naproxen synthesis catalyzed by AMDase-CLGIPL covalently immobilized onto a robust acrylate carrier was investigated with respect to reaction engineering. Kinetic characterization of the immobilized enzyme reveals a KM value of 22.1 ± 0.1 mM in the naproxen malonate conversion and an inhibiting effect of the produced naproxen with a Ki of 26.3 ± 1.4 mM. However, an effective process can be realized without in situ product removal yielding (S)-naproxen with an ee of 99%. By optimizing the product work-up, an isolated yield of 92% was achieved with total turnover numbers between 83,000 and 107,000 in five repetitive batches. Furthermore, process monitoring with in-line Raman spectroscopy was successfully applied to analyze the reaction progress with a root mean square error of prediction of 0.8 mM (corresponding to 4%).
DDC Class
540: Chemie
620: Ingenieurwissenschaften
More Funding Information
Financial support from the Deutsche Bundesstiftung Umwelt (DBU, eng. German Federal Environmental Foundation), grant no. AZ30818-32, is gratefully acknowledged.