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The design and development of efficient biocatalytic cascades and biosynthetic pathways for the sustainable production of amines

Description du projet

Concevoir des enzymes efficaces pour l’industrie chimique

Les amines chirales jouent un rôle essentiel en tant qu’éléments constitutifs des médicaments pharmaceutiques, des substances chimiques nobles et des composés bioactifs. L’utilisation d’amines déshydrogénases (AmDH) dans la synthèse d’amines chirales a suscité un grand intérêt en raison de leur potentiel à surmonter les limites des approches chimiques traditionnelles. Le projet BIOSUSAMIN, financé par le Conseil européen de la recherche, s’est fixé pour objectif de surmonter les limites liées à la stabilité des AmDH, à l’activité catalytique et à la diversité des substrats. Les chercheurs auront recours à des techniques d’ingénierie des protéines pour créer de nouvelles AmDH qui produisent une diversité d’amines et de dérivés avec des rendements élevés et des propriétés chimiques précises. Cette approche permet d’utiliser des ressources renouvelables et de réduire l’incidence environnementale au minimum, l’eau étant le seul sous-produit.

Objectif

The objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.

Régime de financement

ERC-STG - Starting Grant

Coordinateur

UNIVERSITEIT VAN AMSTERDAM
Contribution nette de l'UE
€ 1 461 840,00
Adresse
Spui 21
1012WX Amsterdam
Pays-Bas

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Région
West-Nederland Noord-Holland Groot-Amsterdam
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 1 461 840,00

Bénéficiaires (2)