PROZYMES

Bridging Between Organocatalysis and Biocatalysis: The Powerful Enamine Mechanism of Organocatalysts Engineered into the Tautomerase Superfamily Scaffold

Coordinatore	RIJKSUNIVERSITEIT GRONINGEN    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	2˙000˙000 €
EC contributo	2˙000˙000 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2009-StG
Funding Scheme	ERC-SG
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-05-01   -   2015-04-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	RIJKSUNIVERSITEIT GRONINGEN  Organization address address: Broerstraat 5 city: GRONINGEN postcode: 9712CP contact info Titolo: Dr. Nome: Gerrit Jan Cognome: Poelarends Email: send email Telefono: +31 50 3633354 Fax: +31 50 3633000	NL (GRONINGEN)	hostInstitution	2˙000˙000.00
2	RIJKSUNIVERSITEIT GRONINGEN  Organization address address: Broerstraat 5 city: GRONINGEN postcode: 9712CP contact info Titolo: Mr. Nome: H.D. Cognome: Veldhuis Email: send email Telefono: +31 50 3634142 Fax: +31 50 3634500	NL (GRONINGEN)	hostInstitution	2˙000˙000.00

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 Obiettivo del progetto (Objective)

Proline and related secondary amines were found to be efficient organocatalysts of aldol, alkylation, Michael addition, and other challenging bond-forming reactions. The design of even more efficient systems that would allow extending this remarkable catalytic strategy to a useful and environmentally benign synthetic methodology would be highly desirable. This proposal aims to develop a new class of biocatalysts that use the powerful proline-based enamine mechanism of organocatalysts but that take advantage of the water solubility and stereochemical control available with enzymes. As a scaffold for engineering, we will exploit the active-site template of the tautomerase superfamily proteins, the only known group of enzymes that has the unique feature of using a N-terminal proline in catalysis. By systematically screening tautomerases for promiscuous carbonyl transformation activities, we aim to demonstrate that Pro-1 residues within these tautomerases can react with carbonyl compounds to give enamine intermediates, and thus may facilitate various bond-forming reactions. The most promising enzymes will be used in directed evolution experiments to enhance the desired activities to a practical level. For this, new screening and selection methods will be developed that allow the efficient passage through protein sequence space. Furthermore, unnatural secondary amines will be introduced by total chemical synthesis. In this way, we envision to generate superior biocatalysts for carbon-carbon bond-forming reactions. The idea of using a protein scaffold in which a catalytic proline is present as nucleophile and that has a unique reactivity to form enamines would be a completely new approach to making carbon-carbon bonds. It does not copy something in Nature, but is based on the synthetic requirements of the desired bond-forming reactions. I believe that this type of approach is the future of enzyme engineering and is the key to more application of biocatalysis in industry.