I-Corps: Bacterial strains based on the separatome of E. coli.

本I-CORPS提案涉及以下声明：为包括生物制药开发在内的应用而进行的生物纯化相关的重大努力。创造一系列定制的大肠杆菌菌株，表达最少的讨厌的蛋白质，将具有商业价值，它们的创造独特地基于大肠杆菌分离学的知识。生产重组产品，特别是治疗药物，在有或没有使用亲和尾来指示纯化的情况下发生。如果没有它，用大肠杆菌生产可能是一个挑战：生物分离步骤的制定有些随意；宿主细胞蛋白的存在降低了分离步骤的效率；总体产量和纯度之间的权衡可能不是最好的。相比之下，使用亲和尾有助于减少色谱空间，但仍然可能受到以下问题的困扰：共吸附/共洗脱蛋白质；去除亲和尾；配体成本。通过开发显示最小污染物池的大肠杆菌菌株，相信可以更经济有效地开发工业相关蛋白质。目前的工作将根据I-Corps支持收集到的潜在客户反馈来确定后续开发的优先级。如果可以发现一个强大的商业模式，该团队计划在一个新成立的企业中开展这项活动。

This I-CORPS proposal addresses the following statement: Significant effort is associated with the purification of a biological for applications which include biopharmaceutical development. Creating a series of custom strains of Escherichia coli that express minimized sets of nuisance proteins will be of commercial value, with their creation uniquely based on knowledge of the separatome of E. coli. Producing recombinant products, therapeutics in particular, occur with and without the use of an affinity tail to dictate purification. In its absence, production with E. coli can be a challenge: bioseparation steps are developed somewhat arbitrarily; the presence of host cell proteins reduces separation step efficiency; and the tradeoff between overall yield and purity may not be best. Contrastingly, the use of an affinity tail helps reduce the chromatographic space but still can be plagued by: co-adsorbing / co-eluting proteins; removal of the affinity tail; and ligand cost. By developing E. coli strains that display a minimal contaminant pool, it is believed that industrial-relevant proteins can be developed more cost-effectively. The current effort will prioritize subsequent development based on potential customer feedback collected as a result of I-Corps support. If a strong business model can be discovered, the team plans to pursue this activity in a newly-formed venture.