Exploring the computing power of microbes that shapes the environment

Microbes process input information into output responses through diverse genetic and metabolic mechanisms, effectively making them physical systems that compute. These computations profoundly shape the environment, from driving key chemical cycles in the soil to influencing the planet’s atmosphere. Yet the complexity of natural microbial computations remains poorly understood, including the symbolic representation of information and the underlying algorithmic principles. Synthetic biology provides tools to implement simple but effective genetic circuits in living cells, enabling human-defined computations. These are typically Boolean gates and circuits for combinatorial input processing, but they also include sequential logic, memory-based systems, analog circuits, and distributed computations in cellular consortia. Twenty-five years after the first synthetic genetic circuits were built, the field is now exploring new approaches to move closer to the computing power of natural microbes. With a focus on bacteria, this review examines both natural and synthetic functions with the aim of bridging the complexity gap between them and argues that understanding and formalizing the ways in which microbes compute may be essential for improving synthetic genetic circuitry.