(582bs) Frontier Manufacturing: Scaling Up Synthetic Biology

Authors: 
Polizzi, K. M., Imperial College London
Hallett, J. P., Imperial College
Kontoravdi, C., Imperial College London
Shah, N., Imperial College London



Synthetic biology has the potential to revolutionise the way we make a host of consumer products from materials and energy to food and medicine. In order for this impact to be realised, we must find the best way to translate laboratory discoveries into operating industrial production processes. The challenge here is to transition from existing factories into the factories of the future. 

Today many consumer products are made from fossil resources using synthetic chemistry techniques. In the future we will need to reduce our dependence on petroleum products and move to renewable resources. At the same time, the advent of synthetic biology techniques for rapidly tailoring biological systems for manufacturing purposes will allow us to transition away from synthetic chemistry and into more environmentally friendly production mechanisms using cells. We will tackle the question of how to undergo this transition smoothly by working with our industrial partners on real-world applications in two consumer areas (therapeutics and chemicals manufacturing). 

Developing these future biofactories will require the invention of some new generalised technologies to underpin the new manufacturing processes.  This will draw on our world-class expertise in synthetic biology, biocatalysis, sustainable manufacturing, novel solvents (ionic liquids), and process systems engineering.

We will need new biologically based sensors in order to be able to monitor the production processes as they occur to ensure the product quality (and to allow us to intervene if necessary). We will also need new, more robust production cells that can tolerate the high levels of compounds they make and new microreactors and/or compartmentalisation strategies for using enzymes when whole cells are not required. Because the transition will not happen overnight, we will need to develop intermediate production methods that combine biological and chemical catalysts. This will require solvents that are less toxic to proteins and cells and proteins that are engineered to be more robust in the presence of chemicals. In order to develop processes that are economical and efficient (minimal energy and water usage), we will create computer models to compare alternatives. The most promising processes will be implemented in the factories of our industrial partners. 

We have chosen two challenge areas in which to test our new technologies. The first is healthcare, specifically the manufacture of medicinal compounds and therapeutic proteins. These are already largely made using biological systems, but the existing processes are expensive and complicated. Also, in the future, it would be more efficient to make these medicines as and when they are needed (point-of-care manufacture). Our goals are to make simpler, more cost effective, point-of-care manufacturing systems using a combination of the above mentioned platform technologies: enzyme microreactors, specialised cells, and biosensors. Our second target is to produce bulk chemicals without the need for petroleum inputs. This will require us to adjust our manufacturing techniques for renewable inputs (such as biomass) and to develop new processes that use biology and/or environmentally friendly chemistry to do the conversions. Synthetic biology has never been attempted on such a large scale. Our challenge will be to adapt our parts, devices, and systems to operate at this level. 

We are currently recruiting a large number of postdoctoral researchers to join our team.  If you are interested to hear more about the project, please come by the poster!