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Reconstructing enzymes for novel nitrogen-nitrogen bond forming chemistry

Project description

Tailored enzymatic catalysis of nitrogen-nitrogen bonds

The biological activities of many natural products and pharmaceuticals are often based on nitrogen-nitrogen (N-N) bonds. Since N-N bond formation is difficult to achieve by conventional chemistry, the biosynthetic pathway has attracted great interest and has led to the identification of several enzymes capable of catalysing N-N bond formation. Funded by the European Research Council, the ReCNNSTRCT project aims to develop an enzymatic toolbox for N-N bond formation that relies on natural or redesigned enzymes. Researchers will also delineate the structure of these enzymes and their catalytic mechanisms, paving the way for versatile N-N bond reactions that can be exploited in clinical and research applications.

Objective

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

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2022-STG

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Host institution

RIJKSUNIVERSITEIT GRONINGEN
Net EU contribution
€ 1 500 000,00
Address
Broerstraat 5
9712CP Groningen
Netherlands
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 500 000,00

Beneficiaries (1)