PhD Studentship: Bioprocess: Enzymatic Cascade Driven Asymmetric Reductive Carboxylation

The University of Manchester

Application deadline: 15/05/2026
Research theme: Biocatalysis

How to apply: https://uom.link/pgr-apply-2425

This 4-year PhD studentship is open to Home (UK) and overseas students. The successful candidate will receive an annual tax-free stipend set at the UKRI rate (£20,780 for 2025/26; subject to annual uplift), and tuition fees will be paid. We expect the stipend to increase each year. The start date is October 2026.

We recommend that you apply early as the advert may be removed before the deadline.

This BioProcess_IDLA PhD project will develop tools, knowledge and training in world-class biocatalysis by engineering two distinct cofactor dependent enzymes to yield asymmetric acid building blocks. The widespread UbiD family of prFMN-dependent reversible decarboxylases readily interconvert unsaturated hydrocarbons with the corresponding alpha, beta-unsaturated acid [1,2].

The Leys and Hay groups have been at the forefront of determining the mechanism and of the application of these enzymes. While the corresponding equilibrium is poised towards decarboxylation under ambient conditions, combining UbiD with other enzymes catalysing an irreversible reduction offers scope for CO2 fixation under ambient conditions, as previously demonstrated by coupling ferulic acid decarboxylase (Fdc) to carboxylic acid reductase (CAR) yielding an alpha, beta-unsaturated aldehyde [3].

We seek to expand the scope for UbiD mediated Csp2-H activation by combining Fdc with other enzymes to achieve reductive carboxylation yielding the corresponding saturated acid. The combination of Fdc and selected reductases has scope to afford asymmetric reductive carboxylation by virtue of the regioselective Fdc carboxylation and stereospecific reduction. Combined with biophysical studies (including advanced spectroscopy, computational modelling and structural biology), we will use laboratory evolution to generate variants with suitable properties in terms of substrate scope/activity. The groups of Leys, Green and Hay are co-located in the MIB and have access to relevant world-class infrastructure, Larrosa is housed in recently renovated Chemistry building. The groups are well funded through a range of UKRI/industrial (collaborative) projects and frequently publish joint papers.

Applicants should have, or expect to achieve, at least a 2.1 honours degree or a master’s (or international equivalent) in a relevant science or engineering related discipline.

To apply, please contact the main supervisor, Prof Leys - david.leys@manchester.ac.uk. Please include details of your current level of study, academic background and any relevant experience and include a paragraph about your motivation to study this PhD project.