Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support
Threonine aldolase (TA) from Thermotoga maritima was immobilized on an Eupergit support by both a direct and an indirect method. The incubation time for the direct immobilization method was optimized for the highest amount of enzyme on the support. By introducing the immobilized TA in a packed-bed m...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2013-10-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.9.254 |
| _version_ | 1818655350655549440 |
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| author | Jagdish D. Tibhe Hui Fu Timothy Noël Qi Wang Jan Meuldijk Volker Hessel |
| author_facet | Jagdish D. Tibhe Hui Fu Timothy Noël Qi Wang Jan Meuldijk Volker Hessel |
| author_sort | Jagdish D. Tibhe |
| collection | DOAJ |
| description | Threonine aldolase (TA) from Thermotoga maritima was immobilized on an Eupergit support by both a direct and an indirect method. The incubation time for the direct immobilization method was optimized for the highest amount of enzyme on the support. By introducing the immobilized TA in a packed-bed microreactor, a flow synthesis of phenylserine was developed, and the effects of temperature and residence time were studied in particular. Calculations of the Damköhler number revealed that no mass transfer limitations are given in the micro-interstices of the packed bed. The yield does not exceed 40% and can be rationalized by the natural equilibrium as well as product inhibition which was experimentally proven. The flow synthesis with the immobilized enzyme was compared with the corresponding transformation conducted with the free enzyme. The product yield was further improved by operating under slug flow conditions which is related to the very short residence time distribution. In all cases 20% diastereomeric excess (de) and 99% enantiomeric excess (ee) were observed. A continuous run of the reactant solution was carried out for 10 hours in order to check enzyme stability at higher temperature. Stable operation was achieved at 20 minute residence time. Finally, the productivity of the reactor was calculated, extrapolated to parallel run units, and compared with data collected previously. |
| first_indexed | 2024-12-17T03:08:18Z |
| format | Article |
| id | doaj.art-040f496c98ed4b88942ccac2dd205029 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-17T03:08:18Z |
| publishDate | 2013-10-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-040f496c98ed4b88942ccac2dd2050292022-12-21T22:05:54ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972013-10-01912168217910.3762/bjoc.9.2541860-5397-9-254Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit supportJagdish D. Tibhe0Hui Fu1Timothy Noël2Qi Wang3Jan Meuldijk4Volker Hessel5Micro Flow Chemistry and Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the NetherlandsMicro Flow Chemistry and Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the NetherlandsMicro Flow Chemistry and Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the NetherlandsMicro Flow Chemistry and Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the NetherlandsMicro Flow Chemistry and Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the NetherlandsMicro Flow Chemistry and Process Technology, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the NetherlandsThreonine aldolase (TA) from Thermotoga maritima was immobilized on an Eupergit support by both a direct and an indirect method. The incubation time for the direct immobilization method was optimized for the highest amount of enzyme on the support. By introducing the immobilized TA in a packed-bed microreactor, a flow synthesis of phenylserine was developed, and the effects of temperature and residence time were studied in particular. Calculations of the Damköhler number revealed that no mass transfer limitations are given in the micro-interstices of the packed bed. The yield does not exceed 40% and can be rationalized by the natural equilibrium as well as product inhibition which was experimentally proven. The flow synthesis with the immobilized enzyme was compared with the corresponding transformation conducted with the free enzyme. The product yield was further improved by operating under slug flow conditions which is related to the very short residence time distribution. In all cases 20% diastereomeric excess (de) and 99% enantiomeric excess (ee) were observed. A continuous run of the reactant solution was carried out for 10 hours in order to check enzyme stability at higher temperature. Stable operation was achieved at 20 minute residence time. Finally, the productivity of the reactor was calculated, extrapolated to parallel run units, and compared with data collected previously.https://doi.org/10.3762/bjoc.9.254Eupergitflow chemistryimmobilized enzymethreonine aldolase |
| spellingShingle | Jagdish D. Tibhe Hui Fu Timothy Noël Qi Wang Jan Meuldijk Volker Hessel Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support Beilstein Journal of Organic Chemistry Eupergit flow chemistry immobilized enzyme threonine aldolase |
| title | Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support |
| title_full | Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support |
| title_fullStr | Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support |
| title_full_unstemmed | Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support |
| title_short | Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support |
| title_sort | flow synthesis of phenylserine using threonine aldolase immobilized on eupergit support |
| topic | Eupergit flow chemistry immobilized enzyme threonine aldolase |
| url | https://doi.org/10.3762/bjoc.9.254 |
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