Department of Chemistry,
University of Oxford
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Dr Holly A. Reeve


I am CEO and Co-founder of HydRegen Limited and a Senior Research Lead and Project Manager on a major £2.9m grant awarded to translate the industrially relevant research from my DPhil (PhD) towards commercialisation.

During my DPhil, I demonstrated and developed a highly innovative approach to using cofactor-dependent redox enzymes for H2 driven biotransformations. This system combines the exquisite selectivity of biocatalysts with the perfect atom economy of catalytic hydrogenations and represents a step-change for implementation of biocatalytic processes for fine chemicals synthesis.

We were awarded the "Royal Society of Chemistry Emerging Technology 2013" prize after pitching this research to a highly-respected judging panel which included representatives from industry and academia. This has led to us establishing relationships with large chemical companies such as GSK and Johnson Matthey. To ensure I am equipped to support the business side of this research I have completed business and entrepreneurship training.

holly.reeve@chem.ox.ac.uk

Employment
Jan 2020 - CEO and Co-founder, HydRegen Limited
HydRegen Limited will commercialise the technology developed at the University of Oxford.
Jan 2016 - Senior research lead and Co-Investigator, HydRegen Project, Vincent Group, Uni. of Oxford
To translate our H2-driven biocatalysis system towards market, research spanning enzyme scale-up, optimisation of the enzyme-modified particles, development of biocatalytic hydrogenation steps in industry standard batch and flow reactors and investigation into the scope of the system is required. I am leading this research effort and ensuring developments are industrially relevant by regularly meeting with our industrial Advisory Board and industrial and academic project partners.
June 2015 - August 2015EMBO Short-Term Fellowship, Lenz Group, Technical University, Berlin, Germany
I was awarded a short-term fellowship by EMBO for research into the mechanism of the hydride transfer NAD+/NADH cycling flavo-enzymes. During the 3 month placement I used cloning methods to generate variants of a NAD+-reducing soluble hydrogenase for analysis within the Vincent Group. I learnt a range of molecular biology techniques adding to my scientific repertoire.
March 2015 - Dec 2015Postdoctoral Research Associate, Vincent Group, Uni. of Oxford
I was employed on a GSK-linked project for several months, developing C=C reductions using GSK-relevant enzymes. I supervised 5 undergraduate and graduate student projects, contributed to academic publications, helped develop a business plan for the H2-driven particle system and co-wrote grant applications to support this area of research in the future
Education
Feb 2011 - March 2015 DPhil in Inorganic Chemistry at Jesus College, Vincent Group, University of Oxford
I developed two novel methods to simplify the use of cofactor-dependent enzymes with a focus on enabling enzyme-catalysed chemical synthesis. During my DPhil I balanced research, supervision of 6 Masters students, and a demanding business course. I gave oral and poster presentations at interdisciplinary conferences and was awarded prizes for some of these presentations.
Nov 2012 - June 2013 Science Innovation Plus (SIP) at Saïd Business School, University of Oxford
As part of the SIP course I attended lectures for one module of the MBA, 'Strategy & Innovation', and submitted a technology, markets and organisational capabilities report based on my research, 'HydRegen: License or Manufacture?' While researching this report I gained an in-depth understanding of the interplay between large and small companies in the industrial biotechnology area and how to stay competitive in a rapidly changing environment.
2006 - 2010 MChem at Christ Church, University of Oxford (2.1)
Thesis title: Exploiting enzyme catalysis on electrically conducting particles.
Award: Christ Church Exhibitioner 2007-2010
Grants
2020Entrepreneurial lead: ICURe, SetSquared, up to £35k
2018Principal-Ingestigator: University of Oxford, Public Engagement with Research funding, £4k
2017Co-I and Co-Supervisor: iCASE studentship with Dr Reddy's (PI: Kylie A. Vincent)
2017PI and Supervisor: DTP Research Experience Placement for undergraduate
2016Co-I and Project Manager: EPSRC/BBSRC/Innovate UK, Industrial Biotechnology Catalyst, £2.9m (2016-2020), EP/N013514/1, (PI: Kylie A. Vincent)
2016Supervisor: RSC summer student bursary
2015Fellowship: EMBO Short Term Fellowship
Other experience and positions
PresentCommittee positions: I am passionate about improving communication within the Department of Chemistry, and the Maths Physical and Life Sciences Division, in particular communication to and between postdocs. I sit on a number of committees at Departmental, Divisional and University level. I am currently the Chemistry Voice representative for Oxford Reserach Staff Society (OxRSS) and MPLS RSS.

OUI Innovation Champion
2020 Awarded places on ICURe (SetSquared) and PULSE (BIA and Francis Crick) in 2020
These courses provide in depth entrepreneurship training and mentorship.
2018 Awarded a British Science Association Media Fellowship for 2018 by MPLS
As part of the Fellowship I spent 2 weeks as a Science / Technology journalist at the Mirror Online. I wrote more than 20 articles during this time, including: This experience taught me a great deal about how Universities and research organisations can better interact with the media and provided me with an excellent opportunity to broaden my writing experience and style.
2017Research Fellow: Oxford Innovation Society (OIS) Fellowship Programme awarded; this programme provided training sessions on commercialising research and access to the OIS network
2016Volunteer contributor for Science Innovation Union blog
Publications
J.S. Rowbotham, H.A. Reeve, K.A. Vincent, 'Hybrid Chemo-, Bio-, and Electrocatalysis for Atom-Efficient Deuteration of Cofactors in Heavy Water', ACS Catalysis, 2021, 11, 2596-2604, DOI: 110.1021/acscatal.0c03437

J.S. Rowbotham, A.P. Hardy, H.A. Reeve, K.A. Vincent, 'Synthesis of [4S-2H]NADH, [4R-2H]NADH, [4-2H2]NADH and [4-2H]NAD+ cofactors through heterogeneous biocatalysis in heavy water', J Label CompdRadiopharm., 2021, 1-6, DOI: 10.1002/jlcr.3899

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.202000763https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/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', 2020, Methods in Enzymology, Editor - Kumar, Volume 630, accepted, Link

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

Ash, P.A., Carr, S.B., Reeve, H.A., Skorupskaite, A., Rowbotham, J.S., Shutt, R., Frogley, M.D., Evans, R.M., Cinque, G., Armstrong, F.A., Vincent, K.A.,'Shocking protein crystals into action: combining electrochemistry and infrared microscopy provides insight into [NiFe] hydrogenase mechanism', Diamond Light Source Annual Review, 2017/2018, page 8

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

Ash, P.A., Carr, S.B., Reeve, H.A., Skorupskaite, A., Rowbotham, J., Shutt, R., Frogley, M., Evans, R.M., Cinque, G., Armstrong, F.A., Vincent, K.A., 'A method for generating single metalloprotein crystals in well-defined redox states: combined electrochemical control and infrared microspectroscopic imaging of a NiFe hydrogenase crystal', Chem. Commun., 2017, 53, 5858-5861. DOI:10.1039/C7CC02591B

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

Ash, P.A., Reeve, H.A., Quinson, J., Hidalgo, R., Zhu, T., McPherson, I.J., Chung, M., Healy, A.J., Nayak, S., Lonsdale, T.H., Wehbe, K., Kelley, C.S., Frogley, M.D., Cinque, G., Vincent, K.A. 'Synchrotron-based Infrared Microanalysis of Biological Redox Processes under Electrochemical Control' Anal. Chem., 2016, 88, 6666-6671. DOI:10.1021/acs.analchem.6b00898

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., Vincent, K.A., 'Bioelectrocatalysis for Direct Alcohol Fuel Cells' in Z.-X. Liang and T.S. Zhao (Eds.), Catalysts for Alcohol-Fuelled Direct Oxidation Fuel Cells, RSC, 2012. Link

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.

Healy, A.J., Reeve, H.A., Parkin, A., Vincent, K.A. 'Electrically conducting particle networks in polymer electrolyte as three-dimensional electrodes for hydrogenase electrocatalysis' Electrochimica Acta (2011) 56, 28, 10786-10790. Link.

Healy, A.J., Reeve, H.A., Vincent, K.A. 'Development of an infrared spectroscopic approach for studying metalloenzyme active site chemistry under direct electrochemical control' Faraday Discussions. (2011) 148 345 - 357. Link

Patent
Contributor: 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.

Inventor: A patent covering reductive deuteration was filed in 2018
Selected Presentations and Awards

Research Fellow: Oxford Innovation Society (OIS) Fellowship Programme awarded; this programme provides training sessions on commercialising research and provides access to the OIS network (2017)

Poster prize at the BBSRC NIBB Metals in Biology Networking event, York (Dec, 2016)

EMBO Short-Term Fellowship awarded to allow me to carry out my own research project in the Lenz Group, TU Berlin, Germany (June, 2015)
Poster prize at RSC's 'Challenges in Catalysis for Pharmaceuticals and Fine Chemicals' (Nov, 2014)

Invited oral presentation at the 8th Royal Society of Chemistry-Chemical Research Society of India (CRSI) scientific symposium on the Chemical Sciences in Mumbai, India (February, 2014)

Overall winner of 'RSC Emerging Technology 2013': co-presented our technology with Prof Kylie Vincent (June, 2013). The prize includes business mentoring from an experienced panel of judges

1st prize for a poster presented at the RSC 'High value chemicals from Biomass' conference, London (Sept, 2013)

Oral presentation for 10th International Hydrogenase Conference, 'Biotechnologically Relevant Enzyme-Cascades with H2-Driven Cofactor Regeneration', Szeged, Hungary (July 2013)

2nd prize for a poster and flash talk awarded by BASF at 'Celebration of Catalysis', London (Sept 2012)