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

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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.