Fig. 1: Genetic optimizers can ensure maximal cellular performance.

Simulation parameters and further details are provided in Supplementary Section 5. a Population-level production of a target gene is maximized when growth rate and cellular synthesis rate are balanced⁹³. The corresponding optimal concentration of a regulator may depend on both cellular and environmental conditions, and can be automatically adjusted by a genetic optimizer. b Gradient-based optimization can successfully track the time-varying optimum, but cannot be immediately translated to a genetic circuit because it may result in infeasible negative quantities. Decreasing ϵ_x yields faster convergence at the expense of greater control inputs u₁ and u₂. c Calculating u₁ and u₂ based on the trend of x and y ensures convergence to the optimum x^*. In the four panels at right, ϵ_y increases by an order of magnitude going from left to right (leading to slower y dynamics), and the delay t_d increases by an order of magnitude going from top to bottom.