Dynamic control of arabinose and xylose utilization in E. coli

The common bacterium Escherichia coli ( E. coli ) can utilize the pentose sugars arabinose and xylose for growth and energy. When fed both these sugars, the bacterium preferentially utilizes arabinose and only when all the arabinose is exhausted from the media does it start to use xylose. This hierarchical utilization of the two sugars is dictated by two proteins: AraC and XylR. These proteins act as controllers of sugar utilization and dictate the timing and rate of utilization of these sugars. While the biochemical interactions defining individual arabinose and xylose utilization systems are well understood, it is not completely understood how the hierarchical utilization is maintained by the bacterium, and how the regulatory crosstalk between the two systems facilitates this hierarchy. To help answer these questions, in this work, we systematically experimentally characterize the regulatory crosstalk between the two sugar utilization systems. Our work demonstrates extensive interaction between the two sugar systems. Specifically, data from our experiments suggest that the xylose system can regulate arabinose gene expression and consequently, cellular physiology dynamically via promiscuous transport and maybe through cross interactions between regulator and non‐cognate sugar. Put together, we demonstrate that arabinose and xylose utilization networks exhibit an example of distributed control in a biological system. This design likely ensures that the system does not fail under perturbations (mutations). Our results help understand multi‐process control in biological systems and bring to light design criteria for synthetic biology applications.