PhD Studentship - Directed Evolution of a Radical SAM Enzyme

PhD Description: 

In this project, our objective is to use directed evolution to develop modified radical-SAM enzymes that catalyse the modification or rearrangement of pharmaceutical building blocks to yield novel and/or valuable metabolites. 

Nature uses enzymes to catalyse the formation of valuable compounds for life under a very wide range of conditions, but sometimes we would like to make alternative products.  Directed evolution uses molecular biology to generate mutants that produce an enzyme with modified substrate specificity or selectivity, that yield novel, interesting and valuable reaction products^1,2. For example, novel bio-transformations are seeing increased application in the pharmaceutical industry. Biological catalysis is regarded as ‘green’ chemistry (using clean aqueous media, low temperatures with high energy efficiency). 

Radical SAM enzymes are a family of remarkable enzymes that utilise a radical intermediate to catalyse highly unusual and demanding chemistry, including functionalisation of unactivated C-H bonds and rearrangement reactions^3,4.

The project will require a highly interdisciplinary approach, using a wide range of techniques including molecular biology, biochemistry and chemistry. Enthusiastic candidates with practical experience in one or more of these disciplines are encouraged to apply and for the successful candidate, tuition in new techniques will be provided. 

References. 

1. Turner, N. J. Nature chemical biology5, 567-573, doi:10.1038/nchembio.203 (2009).

2. Arnold, F. H. Angewandte Chemie57, 4143-4148, doi:10.1002/anie.201708408 (2018).

3. Roach, P. L. Current opinion in chemical biology15, 267-275, doi:10.1016/j.cbpa.2010.11.015 (2011).

4. Challand, M. R. et al.Natural product reports28, 1696-1721, doi:10.1039/c1np00036e (2011).

The project is funded for 3 years and welcomes applicants from the UK and EU who have or expect to obtain at least an upper second class degree in  Chemistry, Biochemistry or related disciplines. Funding will cover fees and a stipend at current research council rates (2018-19) of £ 14,777 per annum.

Due to funding restrictions this position is only open to UK/EU applicants

Applications for a PhD in Chemistry should be submitted online at https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Search

Please ensure you select the academic session 2018-2019 in the academic year field and click on the Research radio button.  Enter Chemistry in the search text field.

Please place Peter Roach in the field for proposed supervisor/project

General enquiries should be made to Prof. Peter Roach at plr2@soton.ac.uk.  Any queries on the application process should be made to pgafnes@soton.ac.uk

Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified