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Enzyme-Mediated Dynamic Combinatorial Chemistry

Project description

Using templates to direct enzymatic synthesis

In nature, biomolecular templates define the outcomes of enzymatic reactions in some of the most fundamental biological processes, such as DNA replication, transcription and translation. The EU-funded ENZYME-DCC project will investigate the possibility of using synthetic (artificial) templates to direct enzymatic reactions and access different products to those formed in nature. The researchers will explore a conceptually new approach to using enzymes for chemical synthesis that involves combining tools and concepts from synthetic chemistry with enzymology. In this new methodology, enzymes catalyse reversible reactions and generate complex dynamic mixtures of interconverting products. Artificial template molecules will then be added to recognise and select the desired products from the mixtures.

Objective

Biomolecular templates define the outcomes of enzymatic reactions in some of the most fundamental of biological processes, such as DNA replication, transcription and translation. In synthetic chemistry, molecular templates have enabled the synthesis of highly complex molecular architectures and interlocked structures. The possibility to use synthetic templates to direct enzymatic reactions and obtain alternative products to those generated in Nature will be investigated in this project. The overall objective of this research programme is to explore a conceptually new approach to the use of enzymes for chemical synthesis and thus establish a new synthetic methodology - Template-Directed Enzyme-Mediated Dynamic Combinatorial Chemistry. We will exploit the inherent reversibility of enzymatic reactions to generate dynamic chemical networks, which can be manipulated via supramolecular interactions with artificial template molecules to promote the preferential synthesis of specific products. To implement this novel concept, we will develop an unprecedented, templated, enzymatic approach to oligosaccharide synthesis. We will explore dynamic systems of interconverting glycans with the goal of accessing unusual or challenging oligosaccharide products. The specific aims are: 1. To achieve templated enzymatic selective synthesis of large-ring cyclodextrins (cyclodextrins (CDs) with more than 8 glucose units). 2. To explore cyclodextrin glucanotransferase-mediated dynamic mixtures of modified CDs, and, using thiol-functionalised CDs, develop a doubly dynamic system that combines reversible transglycosylation with disulfide exchange. 3. To generate phosphorylase-mediated dynamic mixtures of linear α-1,4-glycans and employ templates to achieve length- and sequence-selective synthesis. 4. To establish a fuelled far-from-equilibrium system for continuous large-ring CD synthesis using templates together with a series of interconnected dynamic enzymatic transformations.

Host institution

DANMARKS TEKNISKE UNIVERSITET
Net EU contribution
€ 1 499 993,00
Address
ANKER ENGELUNDS VEJ 101
2800 Kongens Lyngby
Denmark

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Region
Danmark Hovedstaden Københavns omegn
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 499 997,00

Beneficiaries (1)