Genome-reduced cells have a lower number of genes that makes them especially interesting for systems and synthetic biology. Yet, genome reduction entails intense genomic modifications that often result in growth defects or other undesirable phenotypes. Using a suite of tools including adaptive evolution, metabolic modeling, and machine learning, we were able to diagnose and fix a constitutive oxidative stress response occurring in Escherichia coli DGF-298. This strain derives from E. coli ...