Opportunities for online monitoring and control of synthetic organisms using biosensors

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Karen Polizzi, Cleo Kontoravdi, Alireza Behjousiar, Antony Constantinou

Imperial College London, United Kingdom

Synthetic biology has roots in industrial biotechnology and, apart from toy examples used as proof-of-principle, most of the examples of engineered systems will produce commercialisable products such as biofuels, pharmaceuticals, novel materials, or other high-value added products. Successful scale up of synthetic organisms will be required to realise the economic potential of synthetic biology and tools that would aid in the development, scale up or manufacturing processes would have a great impact on the field. The ability to tailor organisms for the synthesis of useful products also allows the ability to input genetic circuits that can be used to report the internal state of the cell. Genetically encoded biosensors are potentially a very powerful strategy for bioprocess development where sample sizes can be very limited and non-invasive monitoring techniques can vastly improve high throughput screening strategies. We are interested in using biosensors based on Frster Resonance Energy Transfer (FRET) as ultra-scaled down assays for bioprocess development, medium formulation, and cell line engineering. Our recent work aims to identify good biochemical targets for online monitoring as well as develop FRET sensors for these metabolites. We believe that FRET sensors for basic metabolites can be used to predict more complex phenotypes, particularly when coupled with in silico metabolic modelling.