Optogenetics for integrated, continuous processes for large-scale chemicals manufacture: Next generation manufacturing through synthetic biology

A major limitation of current manufacturing methods using fermentation approaches is the inability to have real-time and non-invasive, closed loop feedback control of the producing organism during long fermentations (e.g. continuous and fed-batch). The ability to monitor quantitatively product formation of volatile products in the headspace and then use this information to regulate production pathways in the host to adjust to desired levels would provide stability and predictability in manufacturing pipelines for chemicals, fuels and materials using engineering biology approaches.

We aim to address this urgent need for volatile products whose build up in a reactor can be cytotoxic. There therefore needs to be 'on-the-fly' real-time control of terpene concentration and active removal of the product by on-line product capture (e.g. sparging; phase separation and related methods). We have in the Scrutton group develop downstream processing methods for active product removal but missing is the ability to capture real-time data on product levels and use of this information to offer feedback control strategies for use with the producing organisms/metabolic pathways.

We plan to achieve this using optogenetic methods where the read out of a mass spectrometer is used to regulate organisms/pathways by direct control of bioreactor LEDs for optogenetic regulation of the producing organism. If made to work this technology would be a game changer for manufacturing using Engineering Biology platforms, offering new routes to stable and predictable manufacture with real-time and non-invasive control.

The aim is to design and implement next-generation real-time monitoring and feedback control of bioproduction processes for chemicals manufacturing, using light-responsive genetic elements and enzymes. The purpose is to build a generic platform capability, using engineered production strains in the Scrutton group and the ability to rapidly engineer further in SYNBIOCHEM/FutureBRH.

The 2016 UK Roadmap Bio-design for the Bio-economy highlighted the substantial impact that synthetic biology can bring to the UK and global economies by developing: frontier science and technology; establishing a healthy innovation pipeline; a highly skilled workforce and an environment in which innovative science and businesses can thrive. Synthetic biology promises to transform the UK Bio-economy landscape, bringing bio-sustainable and affordable manufacturing routes to all industrial sectors and will ensure society can tackle many contemporary global Grand Challenges including: Sustainable Manufacturing, Environmental Sustainability Energy, Global Healthcare, and Urban Development. Whilst synthetic biology is burgeoning in the UK, we now need to build on the investments made and take a further lead in training next generation scientists to ensure sustained growth of a capable workforce to underpin the science base development and growth in an advanced UK bio-economy.
This training provided by this CDT will give students from diverse backgrounds a unique synthesis of computational, biomolecular and cellular engineering skills, a peer-to-peer and industrial network, and unique entrepreneurial insight. In so doing, it will address key EPSRC priority areas and Bioeconomy strategic priorities including: Next-generation therapeutics; Engineered biomaterials; Renewable alternatives for fuels, chemicals and other small molecules; Reliable, predictable, and scalable bioprocesses; Sustainable future; Lifelong health & wellbeing.
Advances created by our BioDesign Engineering approach will address major societal challenges by delivering new routes for chemical/pharma/materials manufacture through to sustainable energy, whilst providing clean growth and reductions in energy use, greenhouse gas emissions and carbon footprints. Increased industry awareness of bio-options with better civic understanding will drive end-user demand to create market pull for products. The CDT benefits from unrivalled existing academic-industry frameworks at the host institutions, which will provide direct links to industrial partners and a direct pathway to early economic and industrial impact.

This CDT will develop 80-100 next-generation scientists and technologists (via the funded cohort and wider integration of aligned students at the three institutions) as adept scientists and engineers, instilled with technical leadership, who as broadly trained individuals will fill key skills gaps and could be expected to impact internationally through leadership roles in the medium term. Importantly the CDT addresses key skill-gaps identified with industry, which are urgently required to create and support high value jobs that will enable the UK to compete in global markets. Commercialisation and entrepreneurship training will equip the next generation of visionaries and leaders needed to accelerate and support the creation of new innovative companies to exploit these new technologies and opportunities.

The UK government identified Synthetic Biology as one of the "Eight Great Technologies" that could be a key enabler to economic and societal development. This CDT will be at the forefront of research that will accelerate the clean growth agenda and the development of a resilient circular bioeconomy, and will align with key EPSRC prosperity outcomes including a productive, healthy and resilient nation. To foster wider societal impact, the CDT will expect all students to contribute to public outreach and engagement activities including: open days, schools visits, and science festival events: students will participate in an outreach programme, with special focus on widening participation.

This CDT will contribute to the development of industrial strategy through the Synthetic Biology Leadership Council (SBLC), Industrial Biotechnology Leadership Forum (IBLF), and wider Networks in Industrial Biotechnology and Bioenergy and Professional Institutes.