Anaerobic bacterial fermentation of sugars was a well-established technology in the early part of the 20th century. It had an important role in providing the solvents acetone, butanol and ethanol at industrial scale. The rapid expansion of the petrochemical industries from the 1950s led to it becoming uncompetitive.
The Synthetic Biology Research Centre
Much more recently, there has been a resurgence of interest in anaerobic fermentation and in particular in gas fermentation where the greenhouse gases CO2 and CO together with H2 waste gases are used as the inputs to microbial anaerobic gas fermentation systems to generate, principally, ethanol.
This approach to solvent production does not need farmland, so it does not compete with food production. Ultimately, the hope is that we will be able to harvest greenhouse gases from the atmosphere and convert them through gas fermentation into useful everyday chemicals. Anaerobes are currently limited in the range of solvents and other molecules they can accumulate through gas fermentation. Whereas, aerobes have the potential to synthesise and accumulate a much wider range of molecules.
The SBRC-Nottingham researches both aerobic and anaerobic microbial systems but its primary focus is aerobic gas fermentation. The chosen chassis for this work is Cupriavidus necator. To date, through a variety of synthetic biology approaches we have shown that this chassis can be engineered to make: 1,3 butanediol, mevalonate, isoprene, 3-hydroxyproprionate, isopropanol, acetone and 2,3 butanediol. All of these molecules are currently used in industrial settings. The SBRC’s ambition is to optimise production chassis to make all of these molecules from greenhouse gases and hydrogen.
There is much more optimisation work to do, but we now have a good understanding of the bacterium’s metabolism and physiology. Its attraction is that it has diverse metabolic pathways so the majority of the metabolic infrastructure exists for the bacterium to make a broad array of compounds. However, this very diversity also means the bacterium is able to also utilise the compounds it makes as a source of energy. Our growing understanding of the complexities of C. necator’s gene redundancy means we are now better equipped to design synthetic pathways to important molecules, to better control production and importantly to prevent the bacterium from digesting the products it has just made.
SBRC-Nottingham has developed systems to maintain genetic stability of production organisms, has patented CRISPR/Cas9 technologies to (i) precisely control gene regulation and (ii) facilitate efficient and rapid genome editing in the C.necator. It is conducting systems biology approaches to further understand the complexities of microbial metabolism and is refining genome scale metabolic models to facilitate predictive biology.
The science is not all focused on microbiology and gas fermentation systems. There is a strong theme of Responsible Research and Innovation running through all the work of the SBRC. This is to ensure that there is a strong awareness amongst researchers as well as amongst the public and policy makers that the direction of scientific exploration is informed by society.
The SBRC has generated many outputs including academic papers, trained PhD students, generated a portfolio of patented genome engineering technologies and has delivered many outreach events and RRI workshops. Many of these outputs are summarised in our infographic (see below).
The SBRC has many industrial and academic collaborative links across the world and spanning many research areas from cancer therapy work and health research to sugar and gas fermentation. Its research and training activities have led to company start-up activity in the field of aerobic gas fermentation. So there is a clear path from academic research through to industrial adoption of the technology.
In our search for better medicines to improve healthcare in an ageing population, for safer agrochemicals to aid food production for a growing population and for advanced materials for new technologies, the global demand for molecules based upon a group of relatively simple carbon based molecules (including ethylene, propylene, butadiene and benzene) continues to increase. Sadly current petroleum and natural gas-based supply chains simply can’t continue to expand to meet this burgeoning need. We can only close this increasing gap between supply and demand by innovating and solving serious scientific challenges.
Funded by the BBSRC and EPSRC, the UK Government has initiated the creation of a number of multidisciplinary Synthetic Biology Research Centres (SBRC) charged with the accelerating the realisation of the benefits of the outputs of Synthetic Biology to business and society.
Synthetic Biology and Engineering Biology
Synthetic biology is “the design and engineering of biologically based parts, novel devices and systems as well as the redesign of existing, natural biological systems”. It is an emerging scientific discipline that has arisen through the merger of several core areas of science, principally biology, engineering, chemistry and Information Communication Technology. Engineering Biology is a more recent term which has synthetic biology at its core but which draws on other scientific disciplines as needed to delivery new processes or infrastructures which enable the synthetic organisms or systems to function optimally.
The SBRC-Nottingham will:
- use Synthetic Biology to engineer microorganisms that can be used to manufacture the molecules and fuels that modern society needs in a cleaner and greener way.
- harness the ability of organisms, to ‘eat’ single-carbon containing gases, such as carbon monoxide (CO), carbon dioxide (CO2) and methane (CH4).
When these gases are injected into the liquid medium of fermentation vessels they are consumed by the bacteria and converted into more desirable and useful molecules. Fortunately CO, our initial target, is an abundant resource, and a waste product of industries such as steel manufacturing, oil refining and chemical production. Moreover, it can be readily generated in the form of Synthesis Gas (‘Syngas’), by the gasification (heating) of forestry and agricultural residues and municipal waste.
By allowing the use of all these available low cost, non-food resources, such a process overcomes concerns over the use of land resources that could be used for food production. Furthermore, capturing the large volume of CO (destined to become CO2 once released into the atmosphere) emitted by industry for fuel and chemical production provides a net reduction in fossil carbon emissions. We will also develop new organisms that can grow on the sugar (glucose and xylose) released from the deconstruction of biomass, derived from municipal waste, agricultural residues and specialist crops grown on land that is unsuitable for food production.
The core scientific aims of the SBRC at Nottingham will be to:
microbial cell factories needed for the efficient production of the chemical that are essential for a modern industrial society.
Through effective communication and promotion we will showcase new science and demonstrate how organisms can make important molecules that will take the place of current fossil fuel based feedstocks. We will improve the current public perception of the scientific community and show how innovation can lead to economic and environmental benefits. We are passionate about sustainability and we believe we can share this vision to the rest of the UKs scientific community and the general public who use our products.