Commercialisation of the Tat protein export pathway for biopharmaceutical production

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Over 30% of licensed therapeutic proteins are made in the bacterium Escherichia coli, where 'export' out of the cytoplasm to the periplasm is a favoured strategy. Current export strategies have severe limitations and we have shown that the 'Tat' export pathway has a number of advantages over traditional systems. The research will enable us to fully commercialise a suite of powerful Tat-based platforms:1. We will optimise a previously-described system in which expression of a Bacillus subtilis Tat system in an E. coli tat deletion strain leads to export to the periplasm and then release to the medium. We will calibrate the leaky outer membrane phenotype to achieve the optimal balance of cell robustness vs membrane leakiness.2. We will commercialise a new platform in which biotherapeutics are exported by Tat with disulphide-bonds subsequently formed in the periplasm.3. We will identify new Tat-based systems that operate more efficiently than the E. coli system.