This project develops a completely new way of implementing biocatalysis for industrial biotechnology in clean electrochemical reactors.
Enzymes dependent on the cofactor NADH are used widely in industrial chemical synthesis, particularly for the manufacture of fine chemicals and pharmaceuticals where single enantiomers are often required. Biocatalysis is now a go-to method for generating stereoselective chiral alcohols or amines. The reaction scope for biocatalytic processes has been broadened enormously by large-scale genetic engineering efforts. However, implementation of biocatalytic oxidations and reductions is still compromised by the need for expensive nicotinamide cofactors at stoichiometric levels. During industrial biocatalytic transformations, NADH or NADPH are recycled via coupled enzymatic reactions, typically linked to the sacrificial oxidation of isopropanol to acetone or glucose to gluconolactone, raising issues around product separation and poor atom economy.
Electroenzymatic NAD(P)H and NAD(P)+ recycling represents an attractive alternative for greener chemistry because it allows chemical synthesis to be controlled by electric current (flow of electrons), with coupled oxidations and reductions promising completely atom-efficient overall processes. We have demonstrated enzyme electrodes that give thermodynamically efficient NADH oxidation or NAD+ reduction to the correct cofactor forms, and we have shown that these can be coupled readily to an NADH-dependent enzyme step.
This project builds upon this initial work, seeking to demonstrate biocatalytic electrosynthesis as a broadly applicable platform that can be used for C=C, C=O and C=N bond reductions as well as the oxidation of alcohols.
The student will receive training in the Vincent-Reeve labs (in the Department of Chemistry in Oxford) in using protein electrochemistry, and in handling NAD+ reductase and NAD(P)H-dependent dehydrogenases, enzyme immobilisation and activity measurements. The student will receive basic training in molecular biology and enzyme isolation. S/he will be trained in analytical methods (UV-vis spectroscopy, chiral-HPLC, GC, NMR and mass spectrometry).
The student will receive training in Johnson Matthey’s labs (Cambridge) in how to transfer the enzymatic processes developed in the Vincent-Reeve labs from lab to preparative scale. Different reactors and reaction set ups will be investigated Training will be provided in the different aspects of industrialisation and product commercialisation. The student will also benefit from attending internal research meetings, site meetings and regular seminars organised in topics such as IP, EHS and QC. Johnson Matthey’s broad experience in the field will be very valuable for the student to compare the reaction outputs with conventional ways of running biocatalytic reactions.
How to apply:
If you are interested in applying for a BBSRC iCASE studentship please contact the named supervisor, Holly Reeve (holly. [email protected]
) for further information and to determine whether they would encourage you to apply. Applicants who wish to apply for a BBSRC iCASE studentship should make an enquiry to the Interdisciplinary Bioscience DTP via [email protected]
for advice on making a full and formal application to the University.
Funding notes: This project is funded for four years by the Biotechnology and Biological Sciences Research Council BBSRC. BBSRC eligibility criteria apply (View Website Annexe 1). EU nationals who do not meet BBSRC residence criteria are encouraged to contact the programme administrator to check their eligibility for BBSRC funding before submitting a formal application. Successful students will receive a stipend of no less than the standard RCUK stipend rate, currently set at £15,009 per year, which will usually be supplemented by the industrial partner.