13TSB_SynBio - Rapid Engineering of Cellular Factories

This is a collaborative R&D project, with the goal of demonstrating the rapid creation of bacterial cellular factories. Over the
next 10-20 years the global chemistry using industry is predicted to undergo a major transformation. Driven by the need to
develop processes that are both economically and environmentally sustainable, the industry will increasingly turn to
renewable feedstocks for the manufacture of a growing range of products. It is estimated that by 2020 approximately 20%
of existing chemical processes will be based on Industrial Biotechnology (IB), and advanced synthetic biology and
bioprocesses.

Within this project we intend to combine several novel technologies, including biopumps, riboswitches, and statistical
process optimization to create engineered micro-organisms which are able to selectively import small molecules, convert
them via short synthetic pathways, and export the finished molecules on a whole cell basis. This methodology has the
potential to revolutionize biocatalysis and IB, and additionally constrains the technical risk, as the use of biopumps allows
the optimization of only short synthetic pathways, rather than utilizing an organism's native metabolic pathways from basic
feedstocks. The outputs from this grant will lead to alternative sustainable chemical production process, with the potential
to reduce the reliance on petrochemically derived feedstocks. This research project will also generate technology and
knowledge that will help maintain the UK's competitive edge, and will produce highly trained and skilled research
personnel.

This is a collaborative R&D project, with the goal of demonstrating the rapid creation of bacterial cellular factories. Over the
next 10-20 years the global chemistry using industry is predicted to undergo a major transformation. Driven by the need to
develop processes that are both economically and environmentally sustainable, the industry will increasingly turn to
renewable feedstocks for the manufacture of a growing range of products. It is estimated that by 2020 approximately 20%
of existing chemical processes will be based on Industrial Biotechnology (IB), and advanced synthetic biology and
bioprocesses.

Within this project we intend to combine several novel technologies, including biopumps, riboswitches, and statistical
process optimization to create engineered micro-organisms which are able to selectively import small molecules, convert
them via short synthetic pathways, and export the finished molecules on a whole cell basis. This methodology has the
potential to revolutionize biocatalysis and IB, and additionally constrains the technical risk, as the use of biopumps allows
the optimization of only short synthetic pathways, rather than utilizing an organism's native metabolic pathways from basic
feedstocks. The outputs from this grant will lead to alternative sustainable chemical production process, with the potential
to reduce the reliance on petrochemically derived feedstocks. This research project will also generate technology and
knowledge that will help maintain the UK's competitive edge, and will produce highly trained and skilled research
personnel.

WHO WILL BENEFIT: Platform and fine chemical companies, biotech companies and contract manufacturing organisations
charged with producing fine and platform chemicals on the multi-kilo and -ton scale, in particular the project partner
Synthace. Additionally, many chemical companies that employ biocatalysts, such as DSM, Lonza, BASF and Dr. Reddy's,
could also benefit from the technologies developed here. Similarly, oil companies such as Shell and BP have invested
heavily in synthetic biology programmes to engineer bacteria to produce new biofuels, where new-engineered microbial
factories would be equally important. Any number of these companies could benefit through licensing agreements to use
new systems based on the technologies developed in this project.

HOW WILL THEY BENEFIT: We will actively seek to communicate our findings to the wider community through scientific
meetings and scholarly publications (We consistently publish in top journals such as: JACS, PNAS, Angew. Chem. &
Nature Chem. Biol.). However, in order for the technology we develop to become widely adopted, particularly in industry, it
will be important to first secure any intellectual property rights for all new inventions we discover. As the research
progresses and our relationships with interested commercial partners develop, and whilst working within the conditions of
the grant, we will seek to commercially exploit these new technologies and license on IP for use in industrial-scale chemical
production processes. Improvements in cell line platform development and bioprocess efficiency, generated from this grant,
could lead to alternative sustainable sources for chemical production, and reduce the reliance upon petrochemical
feedstocks, leading to associated potential environmental benefits. This research project will also generate technology and
knowledge that will help maintain the UK's competitive edge and will produce highly trained and skilled research personnel.