The Metabolic Redox Regime of Pseudomonas putida Tunes Its Evolvability toward Novel Xenobiotic Substrates

Some environmental bacteria evolve with new capacities for the aerobic biodegradation of chemical pollutants by adapting preexisting redox reactions to novel compounds. The process typically starts by cooption of enzymes from an available route to act on the chemical structure of the substrate-to-be. The critical bottleneck is generally the first biochemical step, and most of the selective pressure operates on reshaping the initial reaction. The interim uncoupling of the novel substrate to preexisting Rieske nonheme iron oxygenases usually results in formation of highly mutagenic ROS. In this work, we demonstrate that the background metabolic regime of the bacterium that hosts an evolving catabolic pathway (e.g., biodegradation of the xenobiotic 2,4-DNT) determines whether the cells either adopt a genetic diversification regime or a robust ROS-tolerant status. Furthermore, our results offer new perspectives to the rational design of efficient whole-cell biocatalysts, which are pursued in contemporary metabolic engineering.