Transaminase-membrane reactor for intensified chiral amines production
(2024)
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- Abstract
- For the manufacture of active pharmaceutical ingredients, greener synthesis processes of enantiopure amines are needed. Transaminases (TAs) offer promising routes to produce chiral amines with excellent enantioselectivity and in mild conditions. Yet, challenges like unfavorable thermodynamics and poor free enzyme stability remain. Enhancing TAs robustness and shifting the transamination equilibrium towards high product yields, are thus essential. In this context, immobilizing TAs on membranes appears appealing, as it enables simultaneous biocatalysis and product separation in one-pot. Along this line, the main objectives of this thesis are: (i) immobilizing TAs on membranes to develop biocatalytic membranes, (ii) displacing the equilibrium towards the amines asymmetric synthesis and (iii) producing chiral amines in flow mode. First, TAs immobilization on polymeric membranes is investigated. Among the studied routes, the covalent immobilization on functionalized polypropylene enabled to obtain enantioselective biocatalytic membranes yielding high activity and reusability. These biocatalytic membranes are then applied to an industrially relevant reaction. Their ability to catalyze such asymmetric synthesis is demonstrated: enhanced activity and stability with respect to soluble TAs and to benchmark heterogeneous TAs, were obtained. To improve process productivity, product crystallization is employed. This approach allowed shifting the equilibrium and reaching high yields of pure product crystals. Finally, the immobilized TAs are implemented in a flow reactor, intensifying the biocatalytic process. The benefits of such transfer to flow mode are highlighted: the TA immobilization yield and transamination space-time yield were boosted with respect to the batch operations.
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Meersseman Arango, H. (2024). Transaminase-membrane reactor for intensified chiral amines production. https://hdl.handle.net/2078.5/243549