Descrizione del progetto
Ingegnerizzazione di enzimi efficienti per l’industria chimica
Le ammine chirali svolgono un ruolo fondamentale come elementi costitutivi di farmaci, prodotti della chimica fine e composti bioattivi. L’uso delle ammine deidrogenasi (AmDH) nella sintesi di ammine chirali ha destato un notevole interesse per il loro potenziale nel risolvere i limiti degli approcci chimici tradizionali. Il progetto BIOSUSAMIN, finanziato dal Consiglio europeo della ricerca, intende superare le limitazioni associate alla stabilità, all’attività catalitica e alla gamma di substrati delle AmDH. I ricercatori utilizzeranno tecniche di ingegneria proteica per generare nuove AmDH che producano una varietà di ammine e derivati con rese elevate e proprietà chimiche precise. Questo approccio mira a utilizzare risorse rinnovabili e a ridurre al minimo l’impatto ambientale, in quanto l’unico sottoprodotto è l’acqua.
Obiettivo
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.
Campo scientifico
- natural scienceschemical sciencesorganic chemistryalcohols
- natural scienceschemical sciencescatalysisbiocatalysis
- natural scienceschemical sciencesorganic chemistryamines
- natural sciencesearth and related environmental sciencesatmospheric sciencesclimatologyclimatic changes
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
1012WX Amsterdam
Paesi Bassi