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Enzyme-Mediated Dynamic Combinatorial Chemistry

Carlsberg Foundation Young Researcher Fellowships


The goal of my research programme is to develop a fundamentally different approach to the use of enzymes for chemical synthesis. The role of almost all enzymes, both in Nature and in production processes, is to catalyse reactions in one direction to make single products. We propose instead to employ enzymes that catalyse reversible reactions to link together molecular building blocks and generate dynamic mixtures of interconverting products. To obtain specific targets we will add 'molecular templates' around which the desired products will assemble preferentially. These artificial templates will thus allow us to manipulate Nature's catalysts, control what products they generate, and obtain normally inaccessibly molecules and materials.


The implementation of enzyme-mediated processes to replace traditional chemical synthesis in industrial production has been shown to reduce greenhouse gas emissions, energy usage and waste production. This is because enzymatic processes are fast, specific, and take place under mild condition, usually in water. In light of the globally-recognised need to adopt more sustainable practises, the investigation of new ways to exploit enzymes for chemical synthesis is an important challenge. By merging concepts and methodology from synthetic chemistry with enzymology we aim to expand the possibilities for efficient enzyme-mediated processes.


In this project we will develop the technology of Enzyme-Mediated Dynamic Combinatorial Chemistry to synthesise Large-Ring Cyclodextrins. These are unusual nanoscale macrocycles that are built up from glucose monomers and derived from starch, and that are extremely difficult to access using traditional approaches. However, they have great potential to act as biocompatible and biodegradable hosts molecules for stabilisation, delivery and release of functional bioactive guests, such as drugs, diagnostic markers, flavours and aromas. A team of two post-docs and one PhD student will synthesise molecular templates, use these to enzymatically target different large-ring cyclodextrins, and investigate the properties and capabilities of these almost unexplored materials.


Through this project, we will generate an enhanced understanding of reversible enzymatic processes, their manipulation and exploitation. By exploring a different way of utilising enzymes we aim to promote a movement towards the adoption of enzymatic processes to replace chemical synthesis. Expanded use of enzymes in industry could lead to more sustainable, less polluting, and more efficient processes.