Engineering resource allocation in biological systems is an ongoing challenge. Organisms allocate resources for ensuring survival, reducing the productivity of synthetic biology functions. Here we present a new approach for engineering the resource allocation of Escherichia coli by rationally modifying its transcriptional regulatory network. Our method (ReProMin) identifies the minimal set of genetic interventions that maximizes the savings in cell resources. To this end, we categorized transcription factors according to the essentiality of its targets and we used proteomic data to rank them. We designed the combinatorial removal of transcription factors that maximize the release of resources. Our resulting strain containing only three mutations, theoretically releasing 0.5% of its proteome, had higher proteome budget, increased production of an engineered metabolic pathway and showed that the regulatory interventions are highly specific. This approach shows that combining proteomic and regulatory data is an effective way of optimizing strains using conventional molecular methods.

生物系统中的工程资源分配是一个持续的挑战。生物会分配资源以确保生存，从而降低合成生物学功能的生产力。在这里，我们提出了一种工程化大肠杆菌资源分配的新方法通过合理地修改其转录调控网络。我们的方法（ReProMin）确定了最小化的遗传干预集，可以最大限度地节省细胞资源。为此，我们根据其靶标的必要性对转录因子进行了分类，并使用蛋白质组学数据对其进行了排序。我们设计了转录因子的组合去除，以最大程度地释放资源。我们产生的菌株仅包含三个突变，理论上释放其蛋白质组的0.5％，蛋白质组预算更高，工程化代谢途径的产量增加，并表明调节干预具有高度特异性。这种方法表明，结合蛋白质组学和调控数据是使用常规分子方法优化菌株的有效方法。