Details
| Original language | English |
|---|---|
| Pages (from-to) | 531-540 |
| Number of pages | 10 |
| Journal | Reaction Chemistry and Engineering |
| Volume | 2 |
| Issue number | 4 |
| Early online date | 19 May 2017 |
| Publication status | Published - Aug 2017 |
| Externally published | Yes |
Abstract
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%).
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Chemistry (miscellaneous)
- Chemical Engineering(all)
- Chemical Engineering (miscellaneous)
- Chemical Engineering(all)
- Process Chemistry and Technology
- Chemical Engineering(all)
- Fluid Flow and Transfer Processes
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In: Reaction Chemistry and Engineering, Vol. 2, No. 4, 08.2017, p. 531-540.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Reaction engineering of biocatalytic (S)-naproxen synthesis integrating in-line process monitoring by Raman spectroscopy
AU - Aßmann, M.
AU - Stöbener, A.
AU - Mügge, C.
AU - Gaßmeyer, S. K.
AU - Hilterhaus, L.
AU - Kourist, R.
AU - Liese, A.
AU - Kara, S.
N1 - Funding Information: Financial support from the Deutsche Bundesstiftung Umwelt (DBU, eng. German Federal Environmental Foundation), grant no. AZ30818-32, is gratefully acknowledged. We thank Emil Byström (SpinChem AB, Umeå, Sweden) for the kind provision of the rotating bed reactor, and Björn Neuer and Prof. Dr. Gerrit A. Luinstra from the Institute of Technical and Macromolecular Chemistry (University of Hamburg) for 1H NMR purity analysis of (S)-naproxen. We thank tec5 AG (Oberursel, Germany) for providing the Raman spectrometer for the feasibility study and Tim Ramelow for performing the Raman measurements.
PY - 2017/8
Y1 - 2017/8
N2 - 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%).
AB - 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%).
UR - http://www.scopus.com/inward/record.url?scp=85051327242&partnerID=8YFLogxK
U2 - 10.1039/c7re00043j
DO - 10.1039/c7re00043j
M3 - Article
AN - SCOPUS:85051327242
VL - 2
SP - 531
EP - 540
JO - Reaction Chemistry and Engineering
JF - Reaction Chemistry and Engineering
IS - 4
ER -