Project description
Insight into sugar-processing enzymes opens new applications in medicine and biotechnology
Enzymes that produce and degrade oligosaccharides and generate glycoconjugates have a variety of applications in medicine, the food industry and the energy sector for biofuel production. The EU-funded CARBOCENTRE project aims to provide more insight into the active centre of these glycoprocessing enzymes using biochemical and 3D structural analysis approaches. Unveiling the structure of enzymes through theoretical and computational chemistry will aid the design and synthesis of novel inhibitors as lead compounds against diseases such as cancer. Moreover, scientists will discover and optimise new enzymes suitable for various biotechnology and health applications.
Objective
Enzymes that produce and degrade oligosaccharides and glycoconjugates are present in all kingdoms of life. The ability to visualize, modulate and understand these carbohydrate-active enzymes (CAZymes) therefore offers great potential for human health and sustainable industries. To provide a disruptive shift in our understanding, we adopt in this proposal a multidisciplinary approach combining structural biology, enzymology, computational chemistry, organic synthesis, and chemical biology, with major leaders in these fields part of our CARBOCENTRE Synergy Team. Three fundamental strands will specifically target and capture glycoprocessing enzyme active sites. Biochemical and 3-D structural analyses will inform computational dissection of the reaction coordinate of key enzymes for human health and biotechnology processes. Building on our founding work on retaining glycosidases we will also target inverting glycosidases and glycosyltransferases. Following fundamental analyses, our probes will feed research in two major application domains of human health and biotechnology: 1. To provide visualization, diagnosis, and inhibitor assays and clinical lead compounds for enzymes in cancers and genetic diseases (lysosomal storage disorders). 2. To explore the natural diversity of CAZymes and to discover, quantify and optimize new enzymes for food and household applications and for biomass conversion to biofuels. In an iterative cycle, structural biology and enzymology (Davies, York), will inform, through structures of enzymes and enzyme-inhibitor complexes, theoretical and computational chemistry (Rovira, Barcelona), which in turn will guide the design and synthesis (Overkleeft, Leiden), of inhibitors and activity-based probes for ensuing chemical biology studies in the domains of biomedicine and biotechnology.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciencesclinical medicineoncology
- engineering and technologyindustrial biotechnologybiomaterialsbiofuels
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
- agricultural sciencesagricultural biotechnologybiomass
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Topic(s)
Funding Scheme
ERC-SyG - Synergy grantHost institution
2311 EZ Leiden
Netherlands