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 de- sign, model, and implement a biomolecular concentration tracker, in which an output protein tracks the concentration of an input protein. Using synthetic scaffolds built from small, mod- ular protein-protein interaction domains to colocalize a two-component system, the circuit design relies on a single negative feedback loop to modulate the production of the output protein. Using a combination of modeling 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.

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