Discovery and Engineering of New Enzymes for Late Stage Functionalisation

The project aims to discover and engineer novel enzymes (biocatalysts) that can affect regioselective diversification of complex molecules enabling more efficient and environmentally sustainable production of pharmaceuticals which are urgently required to combat disease. For example, many of the leading pharmaceuticals (blockbuster drugs), possess halogen substituents. However, the traditional chemical halogenation methods that are used to introduce halogens lack selectivity and use toxic reagents as well as deleterious solvents, all of which come at significant cost. In this project we will develop more sustainable enzymatic methods to deliver key halogenated pharmaceutical products and other intermediates under mild conditions, in water, utilising more benign reagents and renewable feedstocks. In collaboration with Prozomix Ltd, we aim to: (i) Develop new bioinformatics approaches for mining genomes and metagenomes for new halogenases and other synthetically useful enzymes; (ii) Establish methods for high throughput cloning, expression and screening of these enzymes; (iii) Further engineer and expand the substrate scope of the selected enzymes, increasing the size and complexity of pharmaceutical scaffolds that can be subjected to efficient late-stage regioselective diversification.