Programming Escherichia coli to function as a digital display

Synthetic genetic circuits offer the potential to wield computational control over biology, but their complexity is limited by the accuracy of mathematical models. Here, we present advances that enable the complete encoding of an electronic chip in the DNA carried by Escherichia coli ( E. coli ). The chip is a binary‐coded digit (BCD) to 7‐segment decoder, associated with clocks and calculators, to turn on segments to visualize 0–9. Design automation is used to build seven strains, each of which contains a circuit with up to 12 repressors and two activators (totaling 63 regulators and 76,000 bp DNA). The inputs to each circuit represent the digit to be displayed (encoded in binary by four molecules), and output is the segment state, reported as fluorescence. Implementation requires an advanced gate model that captures dynamics, promoter interference, and a measure of total power usage (RNAP flux). This project is an exemplar of design automation pushing engineering beyond that achievable “by hand”, essential for realizing the potential of biology. Synopsis A complete electronic chip is encoded in Escherichia coli DNA by combining genetic circuit design automation (Cello) with more accurate mathematical models and gates with reduced impact on the host cell. The circuits encode a function used by calculators to turn on segments and display the digits 0–9. A new gate model captures the impact of placing repressible promoters in series and this is used to more accurately predict how to connect NOR gates. A simple mathematical model is introduced that captures the dynamics of gates using only two parameters that describe the characteristic on and off times for the gate. The dynamic model is able to predict the circuit response over 4 days when cells are transitioned between states. When resource utilization crosses a threshold, the circuits are rapidly lost from the cells. Graphical Abstract A complete electronic chip is encoded in Escherichia coli DNA by combining genetic circuit design automation (Cello) with more accurate mathematical models and gates with reduced impact on the host cell. The circuits encode a function used by calculators to turn on segments and display the digits 0–9.