Commercialisation of the Tat protein export pathway for biopharmaceutical production

超过30%的许可治疗蛋白质是在大肠杆菌中产生的，其中从细胞质到周质的“出口”是一种受欢迎的策略。目前的出口战略有严重的局限性，我们已经表明，“达特”的出口途径有一些优势，比传统的系统。这项研究将使我们能够完全商业化一套强大的基于Tat的平台：1。我们将优化先前描述的系统，其中枯草芽孢杆菌达特系统在大肠杆菌中的表达。大肠杆菌达特缺失菌株导致输出到周质，然后释放到培养基中。我们将校准渗漏外膜表型，以实现细胞稳健性与膜渗漏性的最佳平衡。我们将商业化一个新的平台，其中生物治疗药物由达特输出，随后在周质中形成二硫键。我们将确定新的基于Tat的系统，这些系统比E。coli系统。

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.