PhD EastBio: Expanding artificial enzyme catalysis using structural studies at Edinburgh
About the Project
Artificial enzymes act as unique tools to expand the biocatalytic toolbox to include reactions from chemistry that are not found in nature. Using either bioconjugation approaches or genetic code expansion we have shown that a variety of synthetic cofactors (metal complexes(1), thiamine cofactors(2)) can be introduced to inactive protein scaffolds to create enzymes. Initially many of these artificial enzymes have low activities and stereoselectivities. Directed evolution and AI approaches can optimise enzymes using natural components, but their effectiveness is limited when bioconjugation or unnatural amino acids are used, particularly due to the current scarcity of structural data available in databases (including the pdb) and related catalytic data. One of our protein scaffolds – ttSCP – crystallises rapidly making it an ideal system for expanding our structural knowledge of artificial enzymes via high throughput structural studies.
This project will use ttSCP as a structural platform to investigate a variety of artificial metalloenzymes (ArMs) with a range of metal binding ligands and metal centres including Cu, Fe and Pd for C-C bond forming reactions and selective oxidations(3). Both bioconjugation and genetic code expansion routes(1,4) will be explored for ArM design, using a range of unnatural amino acids developed in the Jarvis group. In collaboration with Prof Dominic Campopiano, we will also investigate structure-based routes to optimising and expanding thiamine co-factor containing artificial enzymes(2).
The project would suit a student with an interest in the chemistry and biology interface. Depending on the student’s background, training will be provided in molecular biology, structural biology and bioinorganic chemistry (understanding metal binding of the proteins using methods such as UV-vis, crystallography, NMR), and in the organic chemistry needed for catalytic testing (both synthesis and analysis i.e. HPLC, GC).
Websites:
https://biology.ed.ac.uk/julia-richardson-group
For more information on the project, eligibility and how to apply for the School's PhD programme, please click on the "Visit Institution Website" link.
Please download and complete the mandatory documents from the EastBio “how to apply” website, before proceeding with your application.
Applicants should apply to the PhD in Biological Sciences with Internship programme via the University of Edinburgh’s admissions portal (Euclid) with a start date of 01 October 2027.
Application deadline: 16 November 2026
For more information and to apply visit https://www.findaphd.com/phds/project/eastbio-expanding-artificial-enzyme-catalysis-using-structural-studies/?p200077