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Reconstructing enzymes for novel nitrogen-nitrogen bond forming chemistry

Descrizione del progetto

Catalisi enzimatica su misura dei legami azoto-azoto

Le attività biologiche di molti prodotti naturali e farmaceutici sono spesso basate su legami azoto-azoto (N-N). Poiché la formazione del legame N-N è difficile da ottenere con la chimica convenzionale, la via biosintetica ha suscitato un grande interesse e ha portato all’identificazione di diversi enzimi in grado di catalizzare la formazione del legame N-N. Finanziato dal Consiglio europeo della ricerca, il progetto ReCNNSTRCT intende sviluppare una serie di strumenti enzimatici per la formazione di legami N-N che si basino su enzimi naturali o riprogettati. I ricercatori delineeranno anche la struttura di questi enzimi e i loro meccanismi catalitici, spianando la strada a reazioni versatili del legame N-N che possono essere sfruttate in applicazioni cliniche e di ricerca.

Obiettivo

Nitrogen-nitrogen (N-N) bonds have fascinating structural and functional properties, are ubiquitously found in diverse pharmaceuticals and fine chemicals, and represent important key structural motifs in diverse natural products, endowing them with potent biological activities. However, traditional chemical procedures to synthesize N-N bond-containing compounds are often difficult to realize, costly and environmentally unfriendly. In addition, the formation of intermolecular N-N linkages is particularly difficult and remains a mostly unaddressed problem in chemistry.
ReCNNSTRCT will address this challenge by decoding novel reaction chemistries from the underexploited family of N-N bond-forming enzymes (NNZYMES), while tackling reactions that are difficult to realize by traditional chemical approaches and currently not feasible by enzyme catalysis. As such, ReCNNSTRCT aims to break new ground in chemical synthesis: it will develop an enzymatic toolbox for versatile N-N bond-forming reaction chemistries by exploring naturally promiscuous and redesigned NNZYMES for diverse intra- and intermolecular, as well as non-natural N-N-bond formations. To achieve this, ReCNNSTRCT will combine methodologies from enzyme catalysis and evolution, genome mining and the latest achievements in bioinformatics. In this way, ReCNNSTRCT will not only establish the chemistry performed by the enzymes, it will also elucidate enzyme structures, catalytic mechanisms, and design biocatalytic cascades to showcase the potential of tailored NNZYMES.
ReCNNSTRCT will thus revolutionize our synthetic strategies and aims to substantially contribute to a greener chemical industry by creating versatile catalytic platforms for N-N bond formation, leading to streamlined routes to high-value chemicals. Beyond this groundbreaking direct impact in the field of enzyme catalysis, ReCNNSTRCT will boost the clinical and research environment by providing new biocatalysts for future drug discovery efforts

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

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Meccanismo di finanziamento

HORIZON-ERC - HORIZON ERC Grants

Istituzione ospitante

RIJKSUNIVERSITEIT GRONINGEN
Contributo netto dell'UE
€ 1 500 000,00
Costo totale
€ 1 500 000,00

Beneficiari (1)