Functional expansion of the natural inorganic phosphorus starvation response system in Escherichia coli

Phosphorus, an indispensable nutrient, plays an essential role in cell composition, metabolism, and signal transduction. When inorganic phosphorus (Pi) is scarce, the Pi starvation response in E. coli is activated to increase phosphorus acquisition and drive the cells into a non-growing state to reduce phosphorus consumption. In the six decades of research history, the initiation, output, and shutdown processes of the Pi starvation response have been extensively studied. Simultaneously, Pi starvation has been used in biosensor development, recombinant protein production, and natural product biosynthesis. In this review, we focus on the output process and the applications of the Pi starvation response that have not been summarized before. Meanwhile, based on the current status of mechanistic studies and applications, we propose practical strategies to develop the natural Pi starvation response into a multifunctional and standardized regulatory system in four aspects, including response threshold, temporal expression, intensity range, and bifunctional regulation, which will contribute to its broader application in more fields such as industrial production, medical analysis, and environmental protection.