Applying Adaptive Laboratory Evolution to Engineer Platform Strains

Adaptive Laboratory Evolution (ALE) is a powerful technology for developing both compound-specific and platform bioprocessing strains. To leverage the utility of high-throughput sequencing after ALE, sophisticated experimentation is necessary to perform controlled ALE experiments with the goal of understanding the range of phenotypes available and how they arise. The presented work will describe an automated technology built for performing ALE experiments and its application towards highlighted use cases. These ALE use cases include adapting strains to higher tolerance of a desired compound, adaptation to utilize non-natural substrates, and adaptation to various bioprocessing conditions.  The genomic changes which enable such adaptation will also be discussed along with interpretation of optimal phenotypes using genome-scale modeling and omics data characterization.  ALE use is increasing in industrial biotechnology and sophisticated platforms for conducting experiments and analyzing outcomes will be necessary to make it a viable technology in the strain generation pipeline.