Public Thesis Defense - IMCN

Transaminase-membrane reactor for intensified chiral amines production by Hippolyte MEERSSEMAN ARANGO

Pour l’obtention du grade académique de Doctorat en Sciences agronomiques et Ingénierie biologique

For the manufacture of active pharmaceutical ingredients, greener processes for enantiopure amines synthesis are needed. Transaminases (TAs) offer promising routes to produce chiral amines with excellent enantioselectivity and in mild conditions. Yet, challenges such as unfavorable thermodynamics and poor free enzyme stability remain. Thus, enhancing TAs robustness and shifting the transamination equilibrium towards high product yields are 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 the industrially relevant asymmetric synthesis of R-2-fluoromethylbenzylamine. As compared to soluble TAs and to benchmark heterogeneous TAs, enhanced activity and stability were obtained. To improve process productivity, in situ product crystallization is employed. This approach allowed shifting the equilibrium and reaching high yields of pure product crystals.

Finally, the membrane-immobilized TAs are implemented in a flow reactor. As compared to batch operations, the TA immobilization yield and transamination space-time yield were markedly boosted, demonstrating an important step towards intensified biocatalytic synthesis processes.

Jury members :

• Prof. Damien Debecker et Prof. Tom Leyssens (UCLouvain) (Promoteurs)
• Prof. Arnaud Delcorte (UCLouvain) (Président)
• Prof. Patricia Luis Alconero (UCLouvain)
• Prof. Francesca Paradisi (University of Bern, Switz.)
• Prof. Jan von Langermann (University of Magdeburg, Germ.)

Pay attention : the public defense of Hippolyte MEERSSEMAN ARANGO will also take place in the form of a videoconference

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