is an innovative, early-stage technology currently under development within the group of Prof. Kylie Vincent at the University of Oxford. Prof Kylie Vincent and Dr Holly Reeve have been awarded £2.9 M from the Industrial Biotechnology Catalyst (Innovate UK/EPSRC/BBSRC), for a 5 year, translational research project, to take the HydRegen
technology towards market.
technology provides a flexible platform of enzyme-modified carbon particles which facilitate implementation of cofactor-dependent biocatalysis for chemical synthesis. This technology has a wide range of applications in the fine chemicals sectors for synthesis of pharmaceuticals, flavour and fragrance molecules and more broadly in introduction of chiral centres and for controlled oxidations.
The concept has been proven and initial results have been recognised by representatives from industry as demonstrated by HydRegen
's success at the RSC Emerging Technology Competition 2013
and more recently by receiving IB catalyst funding
. We are now establishing an interdisciplinary team spanning biocatalysis, catalytic hydrogenation, flow catalysis and molecular biology to demonstrate the technology to a wider audience under industrially useful conditions.
The science behind the HydRegen Technology
We have developed a system of enzyme-modified carbon beads which combine enzymes for H2
-driven NADH recycling and a selective NADH-dependent biotransformation.
A hydrogenase (green) is able to split H2
into protons and electrons. The hydrogenase has a naturally occurring chain of FeS clusters which allow the electrons from H2
oxidation to be rapidly transferred from the active site to the edge of the protein shell. When the hydrogenase is immobilised onto an electronically conducting carbon particle, the electrons can be channelled into the particle. A second enzyme, an NAD+
reductase (blue), is co-immobilised onto the particle. This enzyme is able to take up electrons and use them for efficient reduction of NAD+
A third, NADH-dependent enzyme (red) can then be immobilised on the same particle. In the presence of H2
the NADH is efficiently recycled. This allows reactions to precede with 100 % atom economy. We find that the third enzyme operates faster when co-immobilised in close proximity to the cofactor recycling system that when it is used in solution. For more detail, see our recent publication
This technology addresses 2 key challenges with implementing NADH-dependent biocatalysis. The use of H2 as a reducing equivalent allows up to 100 % atom efficient biotransformations. Our rapid, one-step enzyme immobilisation method is applicable to most biocatalysts and allows simple removal and re-use of the enzymes.
Left to Right: Elena, Philip, Kylie, Holly, Jack, Lisa and Miguel.
This research is conducted within the Vincent Group
at the University of Oxford and is supported by Oxford University Innovation
and an Industrial Advisory Board.
The Vincent group have received major funding from EPSRC via Innovate UK / EPSRC / BBSRC Industrial Biotechnology Catalyst Round 3. The project, developing H2
-driven enzyme-catalysed chemical synthesis, started in Jan 2016 with Dr Holly Reeve as Project Manager.
Michalis Posidias joined the team to begin his DPhil, his research project looks at operating the enzyme-modified particle system in the reverse direction for H+
recycling to support terminal alcohol oxidation to generate aldehydes. This is funded by a BBSCR iCASE studentship with support from Johnson Matthey Catalysis and Chiral Technologies
Work to extend the H2
-driven cofactor recycling system to NADPH recycling for NADPH-dependent enzymes was supported by a Metals in Biology NIBB Business interaction voucher and GSK.
R&D on this innovation was supported by ERC Proof of Concept Grant 297503 during 2012.
Zor, C., Reeve, H.A., Quinson, J., Thompson, L.A., Lonsdale, T.H., Dillon, F., Grobert, N., Vincent K.A., 'H2
-driven Biocatalytic Hydrogenation in Continuous Flow using Enzyme-Modified Carbon Nanotube Columns', Chem. Commun.,
accepted, 2017, DOI:10.1039/C7CC04465H
Cover Article in Biochemical Journal:
Reeve, H.A., Ash, P.A., Park, H., Huang, A., Posidias, M., Tomlinson, C., Lenz, O., Vincent, K.A., 'Enzymes as modular catalysts for redox half reactions in H2
-powered chemical synthesis: from biology to technology', Biochemical Journal
, 2017, 474
, 215-230 DOI:10.1042/BCJ20160513
Cover Article in ChemCatChem:
Reeve, H.A., Lauterbach, L., Lenz, O., Vincent, K.A. 'Enzyme-Modified Particles for Selective Bio-Catalytic Hydrogenation via H2
-driven NADH Recycling' ChemCatChem
, 2015, 7
, 21, 3480 - 3487 DOI:10.1002/cctc.201500766
Reeve, H.A., Lauterbach, L., Ash, P.A., Lenz, O., Vincent, K.A., 'A modular
system for regeneration of NAD cofactors using graphite particles modified with
hydrogenase and diaphorase moieties' Chem. Commun.
2012, 48 (10), 1589-1591.
Lauterbach, L., Idris, Z., Vincent, K.A., Lenz, O. 'Catalytic properties of the
isolated diaphorase fragment of the NAD+
from Ralstonia eutropha
' PLoS ONE
, 2011, 6, (10): e25939.
A patent covering the HydRegen technology was filed in 2011.
Publication number: WO2013050760 A2