Abstract
Dynamic pathway engineering aims to build metabolic production systems embedded with intracellular control mechanisms for improved performance. These control systems enable host cells to self-regulate the temporal activity of a production pathway in response to perturbations, using a combination of biosensors and feedback circuits for controlling expression of heterologous enzymes. Pathway design, however, requires assembling together multiple biological parts into suitable circuit architectures, as well as careful calibration of the function of each component. This results in a large design space that is costly to navigate through experimentation alone. Methods from artificial intelligence (AI) and machine learning are gaining increasing attention as tools to accelerate the design cycle, owing to their ability to identify hidden patterns in data and rapidly screen through large collections of designs. In this review, we discuss recent developments in the application of machine learning methods to the design of dynamic pathways and their components. We cover recent successes and offer perspectives for future developments in the field. The integration of AI into metabolic engineering pipelines offers great opportunities to streamline design and discover control systems for improved production of high-value chemicals.