Monitoring and dynamically controlling glucose uptake rate and central metabolism

Abstract

The rate of glucose import directly affects the maximum possible flux of central carbon metabolism. However, few tools can directly monitor the cellular glucose uptake rate. Here we report the development of a set of programmable bifunctional glucose uptake rate biosensors (GURBs) for real-time monitoring of glucose uptake rate, which enable the dynamic activation and inhibition of glucose uptake and central metabolism in Escherichia coli. These genetic circuits are used to monitor the glucose uptake rates of strains under different culture conditions. Also, feedback-loop control systems are designed to make cells rely on the glucose uptake rate to tune the target metabolic modules, resulting in a substantial increase of the titers of l-tryptophan, riboflavin and d-lactic acid. The glucose-uptake-rate-responsive genetic circuits developed in this study will serve as an effective tool for the dynamic control of glucose uptake and central metabolism. Glucose uptake is the initial step in cellular metabolism, and its uptake rate directly determines the overall metabolic flow. Here the authors develop a set of programmable bifunctional biosensors for real-time monitoring of glucose uptake rates and dynamic dual control of glucose uptake and central metabolism.