Le glutamate (Glu) est le principal neurotransmetteur excitateur du système nerveux central. Ses analogues peuvent se comporter comme des ligands sélectifs et sont intéressants pour élucider le rôle spécifique des différents types de transporteurs ou de récepteurs du système glutamatergique. Ce travail avait pour objectif de synthétiser de nouveaux analogues fonctionnalisés du Glu en utilisant les aminotransférases en tant que biocatalyseurs de façon à convertir les analogues de l'acide 2-oxoglutarique (KG) en analogues du Glu. La plupart des analogues du KG se sont avéré substrats de l'Aspartate Aminotransférase d'E. coli (AspAT) permettant la préparation stéréosélective des analogues du Glu correspondants. Une étude de modélisation moléculaire a été réalisée afin d'expliquer la spécificité de substrat de l'AspAt. Quatre analogues se sont comportés comme des ligands sélectifs et offrent des perspectives pour le développement de nouveaux analogues actifs dans le système glutamatergique

The use of enzymes, nature´s own catalysts, both isolated or as whole cells to perform chemical transformations is called biocatalysis. As a complement to classical chemical catalysis, biocatalysis can be an environmentally friendly and more economical option in the production and synthesis of chemicals. Research on the application of amine transaminases in synthesis of chiral amines have exploded over the last two decades and interest from the industry is increasing. Amine transaminases are promising catalysts due to their ability to perform reductive amination of ketones with excellent enantioselectivity. For a process to be efficient, high substrate specificity of the applied enzyme is an important factor. A variant of Chromobacterium violaceum amine transaminase that was obtained through rational design has an increased specific activity toward (S)-1-phenylethylamine and a set of 4´-substituted acetophenones. This result makes this variant a promising catalyst for the asymmetric synthesis of similar amines. Amine transaminase catalyzed asymmetric synthesis of amines generally suffers from unfavorable equilibrium. Two methods that include spontaneous tautomerization and biocatalytic amidation for equilibrium displacement have therefore been developed. Efficient assays and screening methods are demanded for the discovery and development of novel amine transaminases. For this purpose, a sensitive fluorescence-based assay that holds promise as a high-throughput screening method was developed. One of the major obstacles for application of enzymes in industrial processes is the instability of the enzyme toward harsh conditions. The stability of Chromobacterium violaceum amine transaminase was investigated and improved using co-solvents and other additives. Co-lyophilization with surfactants was also applied to improve the performance of the same enzyme in organic solvents. / <p>QC 20161017</p>

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