Engineered sensor bacteria evolve master-level gameplay through accelerated adaptation

Abstract

Abstract Gene circuits enable cells to make decisions by controlling the expression of genes in reaction to specific environmental factors 1 . These circuits can be designed to encode logical operations 2–7 , but implementation of more complex algorithms has proved more challenging. Directed evolution optimizes gene circuits 8 without the need for design knowledge 9 , but adjusting multiple genes and conditions 10 in genotype searches poses challenges 11 . Here we show a multicellular sensor system, AdaptoCells, in Escherichia coli, that can evolve complex behavior through an accelerated adaptation to chemical environments. AdaptoCells recognize chemical patterns and act as a decision-making system. Using an iterative improvement method, we demonstrate that the AdaptoCells can evolve to achieve mastery in the game of tic-tac-toe, demonstrating an unprecedented level of complexity for engineered living cells. We provide an effective and straightforward way to encode complexity in gene circuits, allowing for fast adaptation in response to dynamic environments and leading to optimal decisions.

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Identifiers

DOI

10.1101/2022.04.22.489191

Journal

bioRxiv (Cold Spring Harbor Laboratory)

Year

2022