iCASE Studentship with Dr Reddy’s Laboratories Ltd.: Developing ways of implementing biocatalytic hydrogenation reactions in flow

The pharmaceutical and fine chemicals sector is becoming increasingly dependent on biocatalysis for C=O, C=C, and C=N bond reductions in the production of complex chiral chemicals. Almost all enzymes responsible for these reactions depend on reduced cofactors NADH or NADPH. Widely applicable approaches to recycling NAD(P)H and immobilisation of the enzymes are still critically lacking. This project exploits a novel H2-driven method for NAD(P)H recycling with enzymes immobilised on carbon beads to develop a platform approach to implementing biocatalysis in flow reactors, and thus establishes a new way of working that will be of great value in the industrial biotechnology sector.

In the unique H2-driven approach developed by the Vincent group (Department of Chemistry, University of Oxford), a hydrogenase enzyme oxidises H2 and channels electrons into a conductive carbon bead. These electrons are used for NAD+ reduction by an NAD+-reductase, to supply NADH to one of the NADH-dependent enzymes used in C=X bond reductions. Since all the enzymes are co-immobilised on carbon beads, this allows the whole biocatalysis system to be handled as a heterogeneous catalyst.

This project will translate the H2-driven biocatalysis approach into flow reactors, and exploits an excellent fit between Prof Vincent’s group and the industrial partner, Dr Reddy’s. Developing new approaches in flow hydrogenation biocatalysis will require consideration of multiple phase boundaries - solid catalyst, gaseous reagent H2, and liquid substrate phase(s) - and relies on expertise at Dr Reddy’s in chemical engineering, flow catalysis and catalytic hydrogenations.

Prof Vincent has been awarded IB Catalyst translation funding to take H2-driven biocatalysis research towards market and has assembled a highly interdisciplinary team of postdoctoral researchers to work on this. There are currently 5 postdocs with backgrounds in molecular biology, biocatalysis and organic chemistry, who will provide substantial technical support and skills training for the student.

The student will spend at least 12 weeks at the Dr Reddy’s site, Cambridge, UK, under the supervision of Dr Shahed Hussain in the biocatalysis department. The project is also supported by Dr Richard Lloyd (Principal scientist, Biocatalysis) and Dr Tony Warr (Head of Process Technology). The Dr. Reddy’s site has been established as the corporate Centre of Excellence for Chiral Technology and has fully equipped chemistry laboratories for carrying out biocatalysis, organic synthesis, flow chemistry, analytical chemistry alongside facilities for molecular biology and fermentation.

This project is supported through the Oxford Interdisciplinary Bioscience Doctoral Training Partnership (DTP) BBSRC Industrial CASE (iCASE) studentship programme. The student recruited to this project will join a cohort of students enrolled in the DTP’s interdisciplinary training programme, and will be able to take full advantage of the training and networking opportunities available through the DTP. For further details please visit www.biodtp.ox.ac.uk.

Prospective applicants should contact the project supervisor Professor Kylie Vincent ([Email Address Removed]) prior to submitting an application.

Applications for this project will be made via the Oxford Interdisciplinary Bioscience DTP. For further details please visit www.biodtp.ox.ac.uk.

Attributes of suitable applicants:

 Undergraduate degree background in chemistry or biochemistry preferred
 Interest in organic synthesis, pharmaceutical chemistry and/or biocatalysis
 Interest in a collaborative, industry facing project
 Confident communicator (written and in oral presentations)