| EPSRC Reference: |
EP/X014886/1 |
| Title: |
Multifunctional Peroxygenase Catalysis for Synthetic Chemistry |
| Principal Investigator: |
Grogan, Professor GJ |
| Other Investigators: |
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| Department: |
Chemistry |
| Organisation: |
University of York |
| Scheme: |
Standard Research |
| Starts: |
21 August 2023 |
Ends: |
20 August 2026 |
Value (£): |
544,056
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| EPSRC Research Topic Classifications: |
| Catalysis & Applied Catalysis |
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| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
Context of the research: Chemical reactions that add oxygen atoms to molecules (oxidations) are significant for industrial pharmaceutical production but often use harsh reaction conditions or toxic chemical reagents. Enzymes, however, operate under mild, non-toxic conditions to achieve equivalent, and often superior outcomes. Some enzymatic oxidations exploit enzymes called cytochromes P450 ('P450s' or 'CYPs'), which, while selective in their reactions, are also complex, unstable and have poor activity, militating against their application in industry. An alternative family of oxidation enzymes called 'Unspecific Peroxygenases' (UPOs) has recently been discovered that have far superior catalytic performance in terms of stability, activity and simplicity, and they thus have great potential for application in industrial oxidations. In addition to oxidations, we have recently found out that UPOs are also able to catalyze many other chemical reactions owing to a catalytically versatile iron atom on their active site. The application of UPOs to reactions other than oxidation would be very valuable for the development of sustainable reactions in synthetic chemistry outside the field of simply oxidation.
Aims and Objectives: The aim of this project is to explore the applicability of UPOs in synthetic chemistry using a mixture of synthetic chemistry, enzymology, protein engineering and process chemistry. We will clone and express a library of UPOs from a range of organisms and characterise their activities and structures using biochemical methods. We will synthesise a range of precursor molecules against which we will test our new enzymes for a range of non-natural synthetic reactions. We will select the best enzymes and use protein engineering techniques to improve them. We will then apply these improved enzymes in scaled up synthetic reactions to provide valuable molecules of relevance to the pharmaceutical industry. In collaboration with industrial partner GSK, we will use the information gained from the project to provide UPOs tailored for non-natural chemistry for industrial applications.
Applications and benefits: The applications of the research will be in the selective transformations of a range of organic substrates to both furnish intermediates and also catalyse late-stage modification of organic molecules for the production of bioactive compounds. The benefits of creating and applying libraries of adaptable enzyme catalysts will be more selective and sustainable chemical processes for applications in industrial chemistry, and especially in pharmaceutical production.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.york.ac.uk |