Harnessing the Synthetic Capabilities of Microbes for Sustainable Synthesis
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Chemistry
Abstract
The process of aerobic respiration by microorganisms is inherently reductive, and uses molecular oxygen to support
primary metabolism via the electron transport chain. However, under anoxic conditions facultative anaerobes can use small
molecule "terminal electron acceptors" as oxidants to support their metabolic processes. These include sulfoxides, sulfates,
metals, aryl halides, and C=C double bonds, all of which are functional groups of interest to synthetic organic chemists.
Examples of such organisms include the Gram-negative microbe Shewanella onedensis, which respires on DMSO using
the molybdopterin-dependent outer membrane reductase DmsAB, and the pathogenic microbe Pseudomonas aeruginosa,
which respires on Fe3+ ions during colonisation of the human lung. However, despite the chemo- and stereo-selectivity
inherent to many of these enzymatic transformations, their use in synthetic chemistry remains unexplored.
This project will explore the synthetic capabilities of microorganisms and the applications of evolutionary methods to create
new enzymes for use in organic chemistry. In particular, we will focus on reactions that are not possible using traditional
synthetic methods. This will streamline many current routes towards industrially important chemicals, whilst also
diminishing the volume of chemical waste produced and enabling its recyclability.
primary metabolism via the electron transport chain. However, under anoxic conditions facultative anaerobes can use small
molecule "terminal electron acceptors" as oxidants to support their metabolic processes. These include sulfoxides, sulfates,
metals, aryl halides, and C=C double bonds, all of which are functional groups of interest to synthetic organic chemists.
Examples of such organisms include the Gram-negative microbe Shewanella onedensis, which respires on DMSO using
the molybdopterin-dependent outer membrane reductase DmsAB, and the pathogenic microbe Pseudomonas aeruginosa,
which respires on Fe3+ ions during colonisation of the human lung. However, despite the chemo- and stereo-selectivity
inherent to many of these enzymatic transformations, their use in synthetic chemistry remains unexplored.
This project will explore the synthetic capabilities of microorganisms and the applications of evolutionary methods to create
new enzymes for use in organic chemistry. In particular, we will focus on reactions that are not possible using traditional
synthetic methods. This will streamline many current routes towards industrially important chemicals, whilst also
diminishing the volume of chemical waste produced and enabling its recyclability.
Planned Impact
This CDT in Optical Medical Imaging will generate numerous avenues for the realisation of impact spanning training, economic, industrial and academic arenas.
Training: The core of our agenda is to ensure that the UK has a strong and sustained pipeline of future innovators and research leaders in the global sector of healthcare technologies, encompassing the molecular, cellular, preclinical and clinical applications of physical sciences in the priority area of Medical Imaging. We will break down traditional 'barriers' between physical, medical, and clinical sciences, while engendering an entrepreneurial ethos. This will create a new cadre of scientist who are multi-skilled and equipped to meet the challenges of applying new technologies to healthcare provision, and who are trained and ready to "do business".
UK PLC: UK Healthcare must reap the dividend of the current 'revolution' in physical sciences. This training programme will deliver new leading-edge multi and cross-disciplinary training and research in exciting and highly translatable areas of optics, imaging and chemistry with clinical application. Our proposed CDT is driven by a clear industrial and "healthcare pull", it fits squarely with EPSRC goals in the Healthcare and Life Sciences sector. Enabling activities through our CDT will create a new generation of scientists, engineers and technologists with a translational agenda, mind-set and business awareness for the benefit of the UK economy.
Companies and Regulators: All the applicants have major interactions with industry, and many have direct personal experience of spin-off/spin-out companies, patenting and licensing. As the CDT progresses new commercial opportunities will undoubtedly arise - this will provide a fantastic training ground for the CDT Scholars in association with the Business School - and will allow them to gain real-life experience of commercial ventures, exploitation and translation.
Promoting sustained academic excellence: The unification of the £90M Technology and Innovation Centre at the UoS with the UoE physical scientists and engineers will generate a globally unique base for physical sciences training and research in optical technologies from optical nanometrology, super-resolution microscopy through to both fluorescent and vibrational sensors. These will be applied in partnership with the University of Edinburgh, College of Medicine in cross-disciplinary, cross-college, cross-disease applications from 'molecule to man'. The biomedical application of these optical approaches will span acute, chronic and regenerative processes in disease. Hence, this partnership will ensure the establishment of a global beacon with sustained academic excellence from which commercial, industrial and social impact will ensue.
General: Our multidisciplinary programme will provide many opportunities for involvement in public engagement and dissemination and our CDT Scholars will become national champions and advocates for the CDT programme, optical medical imaging and the importance of innovation and entrepreneurship. CDT Scholars will present at National and International Science Festivals and participate in a variety of out-reach activities such as the local 'Researchers-in-Residence Programme' which places postgraduate students in local secondary schools, Café Scientifique presentations, and exhibits in Glasgow Science Centre. Through these activities we will not only communicate our scientific findings, but also spread out enthusiasm for scientific research and translation.
Training: The core of our agenda is to ensure that the UK has a strong and sustained pipeline of future innovators and research leaders in the global sector of healthcare technologies, encompassing the molecular, cellular, preclinical and clinical applications of physical sciences in the priority area of Medical Imaging. We will break down traditional 'barriers' between physical, medical, and clinical sciences, while engendering an entrepreneurial ethos. This will create a new cadre of scientist who are multi-skilled and equipped to meet the challenges of applying new technologies to healthcare provision, and who are trained and ready to "do business".
UK PLC: UK Healthcare must reap the dividend of the current 'revolution' in physical sciences. This training programme will deliver new leading-edge multi and cross-disciplinary training and research in exciting and highly translatable areas of optics, imaging and chemistry with clinical application. Our proposed CDT is driven by a clear industrial and "healthcare pull", it fits squarely with EPSRC goals in the Healthcare and Life Sciences sector. Enabling activities through our CDT will create a new generation of scientists, engineers and technologists with a translational agenda, mind-set and business awareness for the benefit of the UK economy.
Companies and Regulators: All the applicants have major interactions with industry, and many have direct personal experience of spin-off/spin-out companies, patenting and licensing. As the CDT progresses new commercial opportunities will undoubtedly arise - this will provide a fantastic training ground for the CDT Scholars in association with the Business School - and will allow them to gain real-life experience of commercial ventures, exploitation and translation.
Promoting sustained academic excellence: The unification of the £90M Technology and Innovation Centre at the UoS with the UoE physical scientists and engineers will generate a globally unique base for physical sciences training and research in optical technologies from optical nanometrology, super-resolution microscopy through to both fluorescent and vibrational sensors. These will be applied in partnership with the University of Edinburgh, College of Medicine in cross-disciplinary, cross-college, cross-disease applications from 'molecule to man'. The biomedical application of these optical approaches will span acute, chronic and regenerative processes in disease. Hence, this partnership will ensure the establishment of a global beacon with sustained academic excellence from which commercial, industrial and social impact will ensue.
General: Our multidisciplinary programme will provide many opportunities for involvement in public engagement and dissemination and our CDT Scholars will become national champions and advocates for the CDT programme, optical medical imaging and the importance of innovation and entrepreneurship. CDT Scholars will present at National and International Science Festivals and participate in a variety of out-reach activities such as the local 'Researchers-in-Residence Programme' which places postgraduate students in local secondary schools, Café Scientifique presentations, and exhibits in Glasgow Science Centre. Through these activities we will not only communicate our scientific findings, but also spread out enthusiasm for scientific research and translation.
