Harnessing Heat Capacity in Enzyme Catalysis using 3D Printed Polymers - Developing a technology suite for the protein Biotech industry

Lead Research Organisation: University of Bath
Department Name: Biology and Biochemistry

Abstract

Enzyme catalysed reactions are specific and provide very large rate enhancements to chemical reactions that would otherwise essentially not occur. Enzymes are therefore enormously commercially important as well as providing a fundamental physical understanding of new catalytic strategies and novel regulatory approaches that other catalysts cannot use.

The large mass of enzymes potentially provides a well of energy, the heat capacity, that can be used to drive chemical reactions. We have found that subtle changes in macromolecular crowding, viscosity and hydration state can affect the enzymes heat capacity, altering the rate and temperature optimum for catalysis.

We will use artificial peptide-based polymers (Mason) to alter the crowding, viscosity and hydration of model enzymes. We will explore how these polymers can alter enzyme heat capacity in our model systems and we will chemically tune the polymers to deliver specific changes in thermal stability, rate or temperature optimum of catalysis. In the first instance, we will use well defined artificial Heme oxidoreductase enzymes from the Anderson lab that can be simulated and manipulated with ease. We will apply computational simulations to optimise the polymer-enzyme interaction (Kamp).

We will explore our designed systems in 3D printed flow-cells to see if combinations of different polymer environments can be used as part of an engineered process that controls enzyme catalysis in real-time.

The idea that the heat capacity of an enzyme can affect catalysis has only recently emerged. The students findings will therefore directly inform our fundamental understanding of enzyme catalysis and these advances are typically published in high ranking journals e.g. JACS. The student will be applying a novel solution to alter enzyme catalysis that does not directly alter the enzyme in any way and this is a radical departure from other strategies. Combined, the catalysis research is of the highest significance to the community both in terms of the approaches taken but also the theoretical underpinning. The project is very feasible since we will be using well characterised model enzyme systems and to start, known peptide polymers. The supervisory team cover the breadth of enzyme catalysis research and enzyme chemistry.

The cutting-edge nature of the research and the developed background work mean we anticipate high-level publications from the project. There is high potential that the project will generate intellectual property relating to industrial biocatalysis applications and we have this in mind when designing the project. We have existing relevant industrial links (Biocatalysts Ltd) who would provide an ideal interaction partner to disseminate industrially relevant findings or technologies.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R512424/1 01/10/2017 30/09/2021
1942830 Studentship EP/R512424/1 01/10/2017 30/09/2021 Samuel David WINTER