Department of Chemistry
University of Oxford
E:holly.reeve@chem.ox.ac.uk

About HydRegen

HydRegen is an enabling-platform technology that offers cleaner, safer, faster chemical production.

Our technologies blend the exquiste precision of biocatalysis and the intensification made possible by modern chemistry. Uniquely, we can decarbonise biocatalysis and replace toxic metal catalysts, and our technologies are compatible with exisiting chemical infrastructure.

We are focusing on tackling challenges in the fine chemicals sectors for synthesis of pharmaceuticals, flavour and fragrance molecules where our technologies lower energy demands, increase product purity and enable continuous flow reactions.

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 by securing a £2.9m IB catalyst award. We have established an interdisciplinary team spanning biocatalysis, catalytic hydrogenation, flow catalysis and molecular biology to demonstrate the technology under industrially useful conditions and to tackle challenges in scale up of both enzyme production and H2-driven biocatalysis.

What do we do?

Animation about our resarch
What our animation for an introduction to Industrial Biocatalysis and the HydRegen technology.

We have developed a system for H2-powered biocatalysis, allowing NADH-dependent C=X reactions with no waste production.

This technology addresses 3 key challenges with implementing NADH-dependent biocatalysis. The use of H2 as a reducing equivalent allows up to 100 % atom efficient biotransformations, producing minimal waste and simplifying isolation of a pure chemical product. Our rapid, one-step enzyme immobilisation method is applicable to most biocatalysts and allows simple removal and re-use of the enzymes.
We are able to implement biocatalysis as a continuous flow process.



Video / Radio

Meet the researchers
Chemistry World Article/Video: about the HydRegen technology
Radio Show: Cleaner greener method for making lab chemicals


Cover articles

ChemCommun: Flow
ChemCatChem: Full Paper
BiochemJ: Review Paper


Podcast

Oxford Sparks' Podcast with Kylie Vincent: Learning from nature


In the news

Women in Science: Cleaner chemicals
Award-winning HydRegen technology offers path to 'clean, safe' chemical production
Enterprising Oxford Blog article: When can I call myself a science entrepreneur?

The Team

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 extensive expertise in fundamental understanding of metal-containing enzymes - this knowledge, along with the characterisation techniques developed, is essential for development of the HydRegen technology.

Kylie Vincent
Principle Investigator

Holly Reeve
Project Manager / Technology & IP strategy

Miguel Ramirez
Enzyme Scale up

Jack Rowbotham
Heterogeneous biocataylst development

Sarah Cleary
Scale up specialist

Kouji Urata
New technologies

Michele Ruggeri
Flow specialist

Adrian Hery Barranco
Novel process design


Awards

The HydRegen Technology was the Overall Winner at the RSC Emerging Technology Competition on the 5th June 2013.

Kylie was the 'Science and Technology Woman of the Future' in 2011.

Funding

2020 ICURe Scheme - Holly Reeve is Entrepreneurial Lead
The HydRegen pre-spin out has been awarded a place on the ICURe scheme to carry out market validation research. This is lead by Dr Holly Reeve.

2020 BIA PULSE programme - Holly Reeve selected
Holly was selected for the intensive BIA PULSE leadership and entreprenuership training programme developed by the BIA and the Francis Crick Institute, aimed at CEOs and future CEOs of companies in the life sciences.

2019 iCASE studentship
Charlotte Hancox joined the team to begin her DPhil, her research project is funded by a BBSCR iCASE studentship with support from Johnson Matthey.

2017 Public Engagement with Research funding
Holly has been awarded funding by the MPLS division to support public engagement activties . We will develop a series of games, talks and experiments to take to secondary schools and build an online platform to inspire and inform school students about Industrial Biotechnology and the HydRegen technology.

2017 iCASE studentship
Barnabas Poznansky joined the team to begin his DPhil, his research project looks at operating the enzyme-modified particle system in continuous flow. This is funded by a BBSCR iCASE studentship with support from Dr Reddy's.

2016 IB Catalst funding
The Vincent group have received major funding from EPSRC via Innovate UK / EPSRC / BBSRC Industrial Biotechnology Catalyst Round 3 (EP/N013514/1). The project, developing H2-driven enzyme-catalysed chemical synthesis, started in Jan 2016 with Dr Holly Reeve as Project Manager.

2015 iCASE studentship
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+-driven NAD+ 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.

2014 Business Interaction Voucher
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.

2012 ERC Proof of Concept funding
R&D on this innovation was supported by ERC Proof of Concept Grant 297503 during 2012.

Publications

Preprint: Poznansky, B., Thompson, L.A., Reeve, H.A., Vincent, K.A., 'Accelerating Biocatalytic Hydrogenations using the H-Cube Flow Reactor', ChemRxiv, 2020, Link

Preprint: Srinivasan, S.J., Cleary, S.E., Paul, E.P., Ramirez, M.A., Vincent, K.A., 'E. coli Nickel-Iron Hydrogenase 1 Catalyses Non-native Reduction of Flavins: Demonstration for Alkene Hydrogenation by Old Yellow Enzyme', ChemRxiv, accepted, Link

Preissler, J., Reeve, H.A., Zhu, T., Nicholson, J., Urata, K., Lautherbach, L., Wong, L.L., Vincent, K.A., Lenz, O., 'Dihydrogen-driven NADPH recycling in imine reduction and P450-catalyzed oxidations mediated by an engineered O2-tolerant hydrogenase', ChemCatChem, accepted DOI: 10.1002/cctc.202000763

Thompson, L.A., Rowbotham, J.S., Nicholson, J.H., Ramirez, M.A., Zor, C., Reeve, H.A., Grobert, N., Vincent, K.A., 'Rapid, Heterogeneous Biocatalytic Hydrogenation and Deuteration in a Continuous Flow Reactor', ChemCatChem, accepted, DOI: 10.1002/cctc.202000161

J.S. Rowbotham, M.A. Ramirez, O. Lenz, H.A. Reeve, K.A. Vincent, 'Bringing biocatalytic deuteration into the toolbox of asymmetric isotopic labelling techniques', Nature Communications, 2020, 11, 1454, DOI: 10.1038/s41467-020-15310-z

B. Poznansky, L.A. Thompson, S.A. Warren, H.A. Reeve, K.A. Vincent, 'Carbon as a Simple Support for Redox Biocatalysis in Continuous Flow', Org. Process Res. Dev., 2020, Special Issure: Flow Chemistry Enabling Efficient Synthesis. DOI: 10.1021/acs.oprd.9b00410

Thompson, L.A., Rowbotham, J.S., Reeve, H.A., Zor, Z., Grobert, N., Vincent, K.A., Chapter 18: Biocatalytic Hydrogenations on Carbon Supports in 'Nanoarchitectures Built with Carbon Nanotubes and Magnetic Nanoparticles', Methods in Enzymology, Editor - Kumar, 2020, Vol. 630, pp303-325. DOI: 10.1016/bs.mie.2019.10.017

Preprint: Rowbotham, J.S., Lenz, O., Reeve, H.A., Vincent, K.A., 2019, ChemRxiv DOI: https://doi.org/10.26434/chemrxiv.7982864.v1

Cover article in ChemCommun: 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., 2017, 53, 9839-9841 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. Link.

Lauterbach, L., Idris, Z., Vincent, K.A., Lenz, O. 'Catalytic properties of the isolated diaphorase fragment of the NAD+-reducing [NiFe]-hydrogenase from Ralstonia eutropha' PLoS ONE, 2011, 6, (10): e25939. Link.

Patent

A patent covering the HydRegen technology was filed in 2011. Publication number: WO2013050760 A2.
More information about the technology can be found on the Oxford Univerity Innovation webiste.

2 further patents have been filed, with further in preparation.


Contact us



Prof. Kylie Vincent (Principle Investigator):

Dr Holly Reeve (Project Manager/Co-Investigator):
Email: holly.reeve@chem.ox.ac.uk, Tel: +44 1865 282600

Department of Chemistry, Inorganic Chemistry Laboratory,
South Parks Road, Oxford, OX1 3QR, UK