Synthetic Biology
Lead Research Organisation:
University of Oxford
Department Name: Synthetic Biology DTC
Abstract
Industrial biotechnology (IB) applies microorganisms to the production of a wide range of products such as pharmaceuticals and biofuels. Traditional IB strategies, whilst markedly more sustainable than common chemical synthesis practices, often rely on limited resources. For instance, industrial fermentation processes may pose an unsustainable demand on sugar and starch, thereby affecting food crop prices and land availability.
In order for IB to be a useful tool in the green economy, strategies must be developed to enable industrial-scale production without increasing demand on valuable resources. Sustainable IB will therefore require altering the range of traditional feedstocks. One way in which this can be achieved is by using different host organisms as IB platforms.
Bacterially-derived simple cells (SimCells) can be applied to this end. SimCells are a novel chassis for synthetic biology and IB applications. They consist of bacterial cells which are free of a native chromosome and can host designed DNA. A SimCell's 'hardware' is the optimised 'shell' of a cell, which enables specific cellular properties; its 'software' is a piece of engineered DNA, which delivers defined functions. SimCells are at the interface between a whole-cell "host" and cell-free biocatalysis, making them a malleable, broadly applicable platform for a number of engineering applications. As non-replicating entities, SimCells can efficiently allocate most of their cellular resources to defined functions instead of cell growth. Their lack of native DNA also improves their safety and circumvents the difficulties and concerns regarding the use of GMOs in industrial processes.
A substantial body of work has been produced by our group on the development and application of SimCells derived from the bacterium Escherichia coli1. The aim of this project will be to expand the existing SimCell toolbox by developing SimCells from the bacterium Ralstonia eutropha. Due to its ability to grow on a wide range of substrates, ranging from organic compounds to H2/CO2, R. eutropha is a suitable candidate for the sustainable production of compounds such as biofuels and bioplastics. SimCells derived from this bacterial species will inherit the cellular machinery (hardware) that enables this valuable facultative chemolithoautotrophic metabolism. Different genetic programs (software) can then be introduced into the SimCells to direct the sustainable production of industrially relevant compounds. Accordingly, the objectives of the project are divided into two distinct categories: hardware development and software development.
The hardware development portion of the project will focus on the production of high-performing, stable SimCells from bacterial parent cells. This will require the optimisation of the protocol for production and purification of SimCells, originally developed in our group for E. coli. Strategies for the regeneration of energy and enzyme cofactors will be built into the SimCells to allow for stable, long-term biocatalytic performance.
The software development part of the project will focus on the design, implementation and optimisation of genetic programs for the production of industrially-relevant compounds by R. eutropha SimCells. Exploiting their facultative chemolithoautotrophic metabolism, these SimCells will be programmed to execute different biosynthesis pathways sustainably either by fixing atmospheric CO2 or by using simple organic compounds (formate, acetate) as substrates. As proof-of-concept, SimCells will be applied to the sustainable production of ethanol. Once this is attained, the production of longer carbon chain products will be tackled.
Broadly, this project aims to harness the potential of synthetic biology to deliver sustainable industrial biotechnology applications. The proposed research falls within the EPSRC research areas of synthetic biology and bioenergy.
In order for IB to be a useful tool in the green economy, strategies must be developed to enable industrial-scale production without increasing demand on valuable resources. Sustainable IB will therefore require altering the range of traditional feedstocks. One way in which this can be achieved is by using different host organisms as IB platforms.
Bacterially-derived simple cells (SimCells) can be applied to this end. SimCells are a novel chassis for synthetic biology and IB applications. They consist of bacterial cells which are free of a native chromosome and can host designed DNA. A SimCell's 'hardware' is the optimised 'shell' of a cell, which enables specific cellular properties; its 'software' is a piece of engineered DNA, which delivers defined functions. SimCells are at the interface between a whole-cell "host" and cell-free biocatalysis, making them a malleable, broadly applicable platform for a number of engineering applications. As non-replicating entities, SimCells can efficiently allocate most of their cellular resources to defined functions instead of cell growth. Their lack of native DNA also improves their safety and circumvents the difficulties and concerns regarding the use of GMOs in industrial processes.
A substantial body of work has been produced by our group on the development and application of SimCells derived from the bacterium Escherichia coli1. The aim of this project will be to expand the existing SimCell toolbox by developing SimCells from the bacterium Ralstonia eutropha. Due to its ability to grow on a wide range of substrates, ranging from organic compounds to H2/CO2, R. eutropha is a suitable candidate for the sustainable production of compounds such as biofuels and bioplastics. SimCells derived from this bacterial species will inherit the cellular machinery (hardware) that enables this valuable facultative chemolithoautotrophic metabolism. Different genetic programs (software) can then be introduced into the SimCells to direct the sustainable production of industrially relevant compounds. Accordingly, the objectives of the project are divided into two distinct categories: hardware development and software development.
The hardware development portion of the project will focus on the production of high-performing, stable SimCells from bacterial parent cells. This will require the optimisation of the protocol for production and purification of SimCells, originally developed in our group for E. coli. Strategies for the regeneration of energy and enzyme cofactors will be built into the SimCells to allow for stable, long-term biocatalytic performance.
The software development part of the project will focus on the design, implementation and optimisation of genetic programs for the production of industrially-relevant compounds by R. eutropha SimCells. Exploiting their facultative chemolithoautotrophic metabolism, these SimCells will be programmed to execute different biosynthesis pathways sustainably either by fixing atmospheric CO2 or by using simple organic compounds (formate, acetate) as substrates. As proof-of-concept, SimCells will be applied to the sustainable production of ethanol. Once this is attained, the production of longer carbon chain products will be tackled.
Broadly, this project aims to harness the potential of synthetic biology to deliver sustainable industrial biotechnology applications. The proposed research falls within the EPSRC research areas of synthetic biology and bioenergy.
Planned Impact
The emerging and dynamic field of Synthetic Biology has the potential to provide solutions to some of the key challenges faced by society, ranging across the healthcare, energy, food and environmental sectors. The UK government has recently a "Synthetic Biology Roadmap", which presents a vision and direction for Synthetic Biology in the UK. The report projects that the global Synthetic Biology market will grow from $1.6bn in 2011 to $10.8bn by 2016. It highlights that there is an urgent need for the UK to develop the interdisciplinary skills required to take advantage of the opportunities provided by Synthetic Biology.
The challenge to the academic and industrial research communities is to develop new translational approaches to ensure that these potential benefits are realised. These new approaches will range across the design and engineering of biologically based parts, devices and systems as well as the re-design of existing, natural biological systems across all scales from molecules to organisms. The techniques will encompass not only individual cells, but also self-assembled biomimetic systems, engineered microbial communities and multicellular organisms, combining multiple perspectives drawn from the engineering, life and physical sciences.
Realising these goals will require a new generation of skilled interdisciplinary scientists, and the training of these scientists is the primary goal of the SBCDT. Our programme will give the breadth of coverage to produce a "skilled, energized and well-funded UK-wide synthetic biology community", who will have "the opportunity to revolutionise major industries in bio-energy and bio-technology in the UK" (David Willetts, Minister for Universities and Science) in their future careers. This will be made possible through genuine inter-institutional collaboration in partnership with key industrial, academic and public facing institutions.
The potential impact of the SBCDT, and its potential national importance, are very therefore high, and the potential benefits to society are significant.
The challenge to the academic and industrial research communities is to develop new translational approaches to ensure that these potential benefits are realised. These new approaches will range across the design and engineering of biologically based parts, devices and systems as well as the re-design of existing, natural biological systems across all scales from molecules to organisms. The techniques will encompass not only individual cells, but also self-assembled biomimetic systems, engineered microbial communities and multicellular organisms, combining multiple perspectives drawn from the engineering, life and physical sciences.
Realising these goals will require a new generation of skilled interdisciplinary scientists, and the training of these scientists is the primary goal of the SBCDT. Our programme will give the breadth of coverage to produce a "skilled, energized and well-funded UK-wide synthetic biology community", who will have "the opportunity to revolutionise major industries in bio-energy and bio-technology in the UK" (David Willetts, Minister for Universities and Science) in their future careers. This will be made possible through genuine inter-institutional collaboration in partnership with key industrial, academic and public facing institutions.
The potential impact of the SBCDT, and its potential national importance, are very therefore high, and the potential benefits to society are significant.
