Evolution of Microorganisms Using Mutator Plasmids

The directed evolution of microorganisms requires the random introduction of mutations and subsequent selection of improved variants. Traditionally, mutagenesis has been performed using DNA-modifying chemicals or UV radiation. An alternative is the use of so-called mutator strains, which carry defects in one or several DNA repair genes. Such mutator strains have been used for the directed evolution of individual genes on plasmids or phagemids (1 ,2 ). It is well documented that mutator strains can evolve rapidly to produce offsprings with novel phenotypes. However, their application for research or as industrial production hosts has been prevented by their very limited genetic stability.