Understanding and harnessing the hydrogen-dependent carbon dioxide reductase activity of E. coli.

Lead Research Organisation: Newcastle University
Department Name: Sch of Natural & Environmental Sciences


For a sustainable future one challenge to scientists is to think of innovative and inspiring new ideas to tackle waste and encourage recycling. From agricultural waste, to food waste and packaging, and all the way to large-scale industrial pollution, scientists from all areas of expertise have a part to play in finding sustainable solutions.

Gaseous carbon dioxide produced by the energy industry, transport sector and other heavy industries (e.g. steel, concrete) is a well-known and environmentally important waste gas. Reducing carbon dioxide emissions will require a basket of different solutions and biology offers some exciting options. Microscopic, single-celled bacteria are used to living in extreme environments and often perform biochemical reactions that plants and animals cannot do. The usually harmless gut bacterium Escherichia coli, for example, can grow in the complete absence of oxygen. When it does this it digests sugars and produces carbon dioxide and hydrogen as gaseous products. We had a brainwave that we might be able to get this reaction to run backwards instead. Sure enough, when E. coli is placed under a CO2 and H2 atmosphere, and some pressure is applied, then the bacterium takes up the CO2 and converts it into something else.

That something else is formic acid and this finding is potentially an important breakthrough for biotechnology. We can now examine the conversion of CO2 to formic acid in more detail in growing, living cells, and optimise it to work mainly in one direction as a 'hydrogen-dependent CO2 reductase'. We can also think about what the formic acid could be used for - maybe to make methanol or lactate using further adapted bacteria, for example, and we can address some of the key obstacles to making this new discovery useful to a wide range of industries.

Ultimately, the underpinning science, and the applied biotechnology that results, has the potential to help reduce carbon dioxide emissions from a whole range of sources, and to convert that CO2 waste into more useful products. This new biotechnology will one day contribute to a truly circular bioeconomy where waste streams are minimal.

Technical Summary

Escherichia coli has a flexible metabolism that includes the ability to perfom an anaerobic fermentation that ultimately produces CO2 and H2. The gases are produced by a membrane-bound metalloenzyme called formate hydrogenlyase (FHL) comprising a molybdenum-dependent formate dehydrogenase linked, via [Fe-S] proteins, to a [NiFe]-hydrogenase (termed Hyd-3). Our most recent research has focusing on understanding the structure and function of FHL. In a important new development, we have now established that FHL can operate as a highly efficient hydrogen-dependent carbon dioxide reductase (HDCR) that can generate high levels of formate from H2 and CO2. The enzyme is especially efficient when the substrate gases are placed under pressure.

In this current early-stage biotechnology proposal, we have designed bioenegineering experiments that will allow us to address key research questions in the field. We will fully characterise the HDCR activity in growing cells and perform chemical and genetic engineering experiments to validate and optimsie the enzymatic activity. We will explore ideas on how to further bio-process the formate produced from gaseous CO2 into other useful chemicals. Finally, we also propose to consider some of the future challenges that a biological system such as this would face if it were to be deployed in an industrial setting. In particular, solutions to the problems of growing microbes under high levels of carbon monoxide will be explored.

Planned Impact

Who might benefit from this research?

The biotechnology research outlined in this proposal addresses directly the BBSRC's STRATEGIC DELIVERY PLAN. This work is focused on understanding and harnessing a remarkable biological activity capable of reducing CO2 to formic acid directly using hydrogen gas. The enzyme that carries this out is a complex metalloenzyme called formate hydrogenlyase (FHL) that is naturally produced in the model bacterium Escherichia coli.

The programme of work has the long-term view to help BUILD THE BIOECONOMY and will potentially contribute to a SUSTAINABLE and RESILIENT future - especially as it addresses societal grand challenges such as tackling climate change and reducing waste.

The proposal sits squarely in the BBSRC 'BIOENERGY AND INDUSTRIAL BIOTECHNOLOGY' Strategic Priority. The science developed here has the potential to be translated into biotechnology applications that could help utilise waste CO2 as a potential feedstock for other bioprocessing activities. The project connects with several BBSRC NIBB, most notably C1net NIBB (gas fermentation) and Metals in Biology NIBB (metalloenzymes, metal processing). The broad scope of the current project should allow it to retain a high profile in the future BBSRC NIBB landscape.

The BBSRC STRATEGIC DELIVERY PLAN also highlights creative, innovative and pioneering 'FRONTIER BIOSCIENCE', and especially 'EXPLOITING NEW WAYS OF WORKING', as of paramount importance, and this work comprises award-winning academics who will provide new knowledge that can help maintain the UK's prominent position in the area of microbial metabolic and biochemical engineering.

As well as meeting UK government priorities, this project will also be of interest to a large number, and a diverse cross-section, of academic researchers, industrialists, and students of microbiology and chemistry. In addition, organisations and companies worldwide interested in carbon capture and exploring solutions for carbon cycling, bioprocessing, and developing value added bio-products, will benefit.

Finally, those individuals trained as a direct result of their involvement in this diverse research project will benefit enormously at a personal level and the UK science community will benefit as a result of that training in the medium term. The postdoctoral research assistant will have access to training in transferable skills for the purposes of career and personal development. The University of Dundee is committed to such training and mentoring of research staff and employ an Office for Professional Development whose remit is the provision of a range of courses that all postdoctoral researchers are encouraged to attend.

The results and intellectual property from this study will be protected as appropriate before being disseminated at international conferences and in high quality publications.

How might they benefit from this research?

The long-term improvements in carbon capture and recycling are expected to be exciting. It is anticipated CO2 produced by the bioeconomy and bioprocessing sectors could be capitalised upon. New science and innovation around utlization of formate will develop as a result. Heavy industries, such as steel and energy, could sieze the opportunity to take a bio-based approach to carbon capture, especially as biochemical innovation needed to cope with contaminating toxic could be forthcoming.
Description This award included funding for a very special piece of equipment - a pressurised bioreactor. It has taken a long time to figure out how to get the most out of this instrument, but we have been able to show that growing cells can capture CO2 and convert it to formic acid. The optimum pressure for this is a mixture of H2/CO2 at 4 bar. The key finding has now been published in Applied & Environmental Microbiology.
Exploitation Route This will be of use to industrial partners hoping to reduce or eliminate CO2 emissions. Potentially, a biological solution like this could capture carbon as formic acid only, or allow its further conversion in to other products.
Sectors Energy,Environment,Manufacturing, including Industrial Biotechology

Description POC-09-SARGENT-CCnet
Amount £62,020 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2020 
End 09/2020
Description Consultancy - BEIS CCU 2.0 Project 
Organisation Ingenza Ltd
Country United Kingdom 
Sector Private 
PI Contribution Consultant on biotechnology project led by Ingenza.
Collaborator Contribution Project management.
Impact N/A
Start Year 2022
Description REDEFINE:H2E International Future Lab in H2 Energy 
Organisation Technical University of Munich
Country Germany 
Sector Academic/University 
PI Contribution I am an academic partner in an International Network hosted by TU Munich. Research is based in Germany with some light-touch supervisory elements from me.
Collaborator Contribution TU Munich carries out interdisciplinary research on hydrogen energy. Joint publications are expected.
Impact N/A
Start Year 2022
Description Cafe Scientifique 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Invitation to present to Cafe Scientifique (Stockton-on-Tees branch) on 20 October 2020. Event moved on-line due to Coronavirus Pandemic. There were >50 participants on the Zoom session located around the UK. They bought me some cheese from Wensleydale Creamery as a 'thank you'.
Year(s) Of Engagement Activity 2020