Design and implementation of a synthetic biomolecular concentration tracker

As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we design, model, and implement a biomolecular concentration tracker, in which an output protein tracks the concentration of an input protein. Synthetic modular protein scaffold domains are used to colocalize a two-component system, and a single negative feedback loop modulates the production of the output protein. Using a combination of model and experimental work, we show that the circuit achieves real-time protein concentration tracking in Escherichia coli and that steady state outputs can be tuned.