An Automated Adaptive Laboratory Evolution Platform for Industrial Biotechnology

Adaptive Laboratory Evolution (ALE) is a powerful experimental technique that exploits the inherent competition at play within a microbial culture and the natural accumulation of mutations from which to select desired phenotypic traits. Unlike rational engineering approaches, ALE is conducted without a priori knowledge on how such traits would arise and therefore can result in unintuitive biological mechanisms for adapting to desired selection pressures. By automating the ALE process, experiments can be run in high-throughput and with tight control over all environmental and process parameters. Omics characterization of evolved strains following an ALE experiment elucidates the genetic and metabolic changes underlying the new phenotype, with which genome engineering techniques can be used to guide the production or refinement of strains with specific biotechnological applications. We have generated and utilized an automated ALE technology in a number of applications, including maximizing strain growth rate in a given environment, increasing tolerance to inhibitory chemicals, and weaning cells onto new, previously unusable nutrient sources. As the use of ALE increases for both basic research and applied biotechnological goals, it will be important to develop a streamlined process for leveraging this ALE technology to facilitate optimal strain designs and production processes.