Synchronous long-term oscillations in a synthetic gene circuit

Abstract

Synthetically engineered genetic circuits can perform a wide range of tasks but generally with lower accuracy than natural systems. Here we revisited the first synthetic genetic oscillator, the repressilator1, and modified it based on principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. This created highly regular and robust oscillations. Some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them. Our results show that even the simplest synthetic genetic networks can achieve a precision that rivals natural systems, and emphasize the importance of noise analyses for circuit design in synthetic biology.