H-transfer reactions involving hydride, hydrogen atom or proton transfers are ubiquitous in enzyme-catalysed reactions. It is now well established that these reactions can occur via a mechanism involving some degree of quantum mechanical tunnelling (QMT), and thus are a feature of quantum biology. The QMT contribution is highly variable and an open question remains whether there has been evolutionary pressure to select for QMT during enzyme catalysis. In this project we aim to combine experimental studies of H-tunnelling in enzyme catalysed reactions with directed (laboratory) evolution (DE) to provide new insight into the role of QMT during (artificial) evolution of H-transfer enzymes. Further, as efficient routes to selective deuteration of pharmaceuticals is currently a hot topic, and many industrially-important enzymes catalyse H-transfers, the methodology also promises to lead to a new approach to enzyme optimisation for applications in synthesis and industrial biocatalysis.
This post-doctoral position is based in the Manchester Institute of Biotechnology (MIB) and Department of Chemistry at the University of Manchester and aims to map QMT contributions to enzyme reactions along artificial enzyme evolutionary trajectories. This approach will involve the development and use of laboratory DE strategies, advanced enzyme kinetics, kinetic isotope effect (KIE) measurements and structural biology. The successful applicant will work in the research groups of Profs Sam Hay and Anthony Green, which are currently funded by the BBSRC, EPSRC, ERC and other sources, and are well-equipped for a full range of computational, molecular and biophysical techniques.
During the project you will design the methodology for, and perform the directed evolution of H-transfer enzymes using parallel selection methods, measure enzyme activity, kinetics and isotope effects, and potentially perform X-ray crystallography experiments.
Prior experience in the directed evolution of enzymes, the measurement of kinetic isotope effects (KIEs) on enzyme catalysed reactions and/or experience of high-throughput chromatography is highly desirable. Experience in one or more of the following areas would be an advantage:
What you will get in return:
As an equal opportunities employer we welcome applicants from all sections of the community regardless of age, sex, gender (or gender identity), ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
Our University is positive about flexible working – you can find out more here
Hybrid working arrangements may be considered.
Please be aware that due to the number of applications we unfortunately may not able to provide individual feedback on your application.
Please note that we are unable to respond to enquiries, accept CVs or applications from Recruitment Agencies.
Any recruitment enquiries from recruitment agencies should be directed to People.Recruitment@manchester.ac.uk.
Any CV’s submitted by a recruitment agency will be considered a gift.
Enquiries about the vacancy, shortlisting and interviews:
Name: Prof. Sam Hay
Email: Sam.Hay@manchester.ac.uk
General enquiries:
Email: People.recruitment@manchester.ac.uk
Technical support:
0161 850 2004 https://jobseekersupport.jobtrain.co.uk/support/home
This vacancy will close for applications at midnight on the closing date.
Please see the link below for the Further Particulars document which contains the person specification criteria.
