Objective
The filamentous fungus Trichoderma reesei produces two potent cellobiohydrolases, CBHI and CBHII. The two enzymes have different structures but both have active sites located in enclosed tunnels containing constellations of amino acids that interact with each other and the substrate. Our earlier studies and comparisons of the enzymes with homologous cellulases provide narrow structural constraints for proposed catalytic mechanisms and suggest residues whose mutation will alter pH-dependencies. Our objective is examine and engineer the catalytic mechanisms of T. reesei CBHI and CBHII by state of the art methods in molecular and structural biology and bio-organic chemistry. A detailed model of the interaction of a cellulose chain with these enzymes will be generated by crystallographic analysis of mutant enzymes in complex with natural and modified oligosaccharides. Novel mechanistic probes will be used to establish still unknown details of the mechanisms of the wt enzymes, and to delineate changes of mechanism in the engineered proteins. An exhaustive search of interactions in the active site, carried out by making a range of systematically modified inhibitors and probes, together with complementing mutations in the enzymes will lead to iterative improvement of the active site. This will allow us to raise the pH optima of the two enzymes. Cellulolytic enzymes are already used in e.g. textile and paper industry. Genetic engineering, when combined with structural biology and a solid background in enzymology provides powerful means for learning and improving the enzyme function. In this proposal, all these aspects are included making possible significant advances in the understanding and engineering the catalytic mechanisms of cellulases. Since the same catalytic principles apply to a wide range of other glycosidases which also share similar three-dimensional structures and active site topologies, the results of this work have a wide application potential in enzymatic modification of carbohydrates. Better understanding of these enzyme mechanisms provides new product ideas for the existing biotech industries and may well lead to the development of completely new industries. The results will help European industry to utilise renewable resources in the development of novel biodegradable products and processes, and in future production of renewable energy and raw materials.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences catalysis
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural biology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
02044 ESPOO
Finland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.