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

本I-CORPS提案针对以下声明：重大努力与生物纯化相关，用于包括生物制药开发在内的应用。创造一系列表达最小化的滋扰蛋白的大肠杆菌定制菌株将具有商业价值，其创造独特地基于对大肠杆菌分离组的了解。杆菌产生重组产物，特别是治疗剂，在使用和不使用亲和尾来指示纯化的情况下发生。在缺乏该酶的情况下，用E.大肠杆菌是个挑战：生物分离步骤的开发有些随意;宿主细胞蛋白质的存在降低了分离步骤的效率;并且总产率和纯度之间的折衷可能不是最佳的。相比之下，亲和尾的使用有助于减少色谱空间，但仍可能受到以下因素的困扰：共吸附/共洗脱蛋白质;亲和尾的去除;以及配体成本。通过开发E.大肠杆菌菌株显示出最小的污染物池，相信工业相关的蛋白质可以更有成本效益地开发。目前的工作将根据I-Corps支持收集的潜在客户反馈确定后续开发的优先次序。 如果能找到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.