Cellular metabolism is an interconnected network of chemical reactions, each step catalyzed by dedicated enzymes. Inhibition or intentional removal of an enzyme should grind the pathway to a halt, a fact exploited by many drugs. However, given an adequate level of variation, cells inevitably circumvent such roadblocks. Pontrelli et al. challenged a strain of Escherichia coli with increased mutation rates to overcome a blocked biosynthetic pathway for the essential cofactor coenzyme A. Not one, not two, but three independent shortcuts around the roadblock were selected for, each after removal of the former. Such plasticity underlies the well-known ability of microorganisms to evade antibiotics.
