Frontier Manufacturing: Scaling up synthetic biology

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. 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.

The overall outcome will be novel, cost effective, energy efficient, and sustainable routes to therapeutics and chemicals.

The development of synthetic chemistry in the 19th and 20th centuries resulted in many of the major industries of today. These industries largely rely on oil as their basic feedstock. The fragility of oil supply has led a need to reengineer the chemicals industry to use bio-based feedstocks. Synthetic biology can make a major contribution to this.

At Imperial College's Centre for Synthetic Biology and Innovation, together with national and international colleagues, we have been developing platform technologies which are applicable across a range of industrial fields. This comprises novel wet lab techniques for DNA assembly, BioPart characterisation and Host Cell (Chassis) development - as well as a web-based synthetic biology information system (SynBIS) comprising a professional registry of BioParts, Models and BioCAD design tools. Imperial's Departments of Chemical Engineering and Chemistry are both internationally renowned for their industrially-relevant innovation in chemicals manufacturing, process development and design, and the translation of this to industrial application. This project is to address the challenge of taking synthetic biology from the laboratory bench to the chemicals manufacturing plant. We will ensure this by cutting edge research and innovation, translation underpinned by deep industrial user engagement and the development of future leaders, as described in the Case for Support and Pathways to Impact Statement.

We anticipate our work will benefit a wide range of stakeholders including: synthetic biologists, chemical and energy companies, materials manufacturers and the broader chemical industries, as well as consumers interested in new products developed through the exploitation of synthetic biology. Our proposed project will demonstrate to this broad base of stakeholders the opportunities and benefits of novel hybrid chemo-biological processes, and compute performance benchmarks by which novel processes can be compared against existing process chains.

In order to ensure this impact, we have already involved several industrial partners (GSK, Shell, Lonza, Dr Reddy) as initial stakeholders in our research programme. Representatives from each of these companies will be closely involved in helping to shape and critique our activities, advising us on pathways to commercialisation and ensuring we maximise the impact of our research efforts.

As this research is primarily aimed at developing manufacturing processes using synthetic biology, we anticipate a substantial impact on the future landscape of the UK manufacturing sector. The material routes and practices developed in this type of research represent potential economic impact by developing secure routes of material and chemical manufacturing within the UK. Breaking our dependence on fossil reserves will also necessarily create new manufacturing industries and also reduce our dependence on imported goods. Introducing novel synthetic biology practices will also revolutionise the existing manufacturing industries.

There is great training potential within this project. As we will be employing 12 full-time researchers in the programme, we will be furthering the dissemination of synthetic biology principles into the employment sector. This will influence future manufacturing directions as the propagation of these future research and development leaders into industry is inevitable.

The extensive timeline of this programme (five years) will enable us to have a sustained impact on manufacturing practices and policies, as we will be able to extend our vision into industry (through our project partners) and public policy (through our advisory institutes). The value of these goals cannot be overstated - the impact of academic research can only be realized if the support of government agencies and the UK public is evident. This requires long-term commitments to the research principles we have outlined within this programme.