Download the full description of this project: ESR12: Covalent fragments to activate industrial enzymes
As a novel fragment-based application, this project will identify fragments to activate enzymes that are used for chemical conversions in industry and covalently attach the fragments to the enzymes and optimise hit fragments that increase enzyme activity. The student will join a team working on fragment-based methods for activating industrial enzymes.
1. To identify fragments that activate industrial enzymes such as amylase and cellulase.
2. To characterise the kinetics, mechanism of action, substrate and product profiles of enzymes activated by fragments.
3. To design covalent strategies to attach the fragments to the enzymes for biotechnology applications.
The York laboratory has recently demonstrated that small fragments can increase the activity of an enzyme. A project is beginning during 2016 to extend this work in two directions. The first is to identify activators for other enzymes, such as cellulase and glycosidases which are used industrially for pulp processing and bioenergy production. The second is to explore synthetic methods for covalently attaching these activating fragments to the enzyme. This should increase the activity but crucially mean that the compounds are not lost in the industrial process.
The details of the project for the student will be decided during the summer of 2016 but will also be tuned to the interests and aptitude of the student. If the primary interest is synthetic chemistry, then there are a number of different attachment strategies to be explored, including some new ideas in this area of bio-orthogonal chemistry. If the primary interest is fragment-based discovery and enzyme activation, then there are a number of industrial enzymes that are being prepared for study.
1. Darby et al. Angewandte Chemie, 2014, 53, 13419-13423.