Untargeted metabolomics links glutathione to bacterial cell cycle progression

Cell cycle progression requires the coordination of cell growth, chromosome replication, and division. Consequently, a functional cell cycle must be coupled with metabolism. However, direct measurements of metabolome dynamics remained scarce, in particular in bacteria. Here, we describe an untargeted metabolomics approach with synchronized; Caulobacter crescentus; cells to monitor the relative abundance changes of ~400 putative metabolites as a function of the cell cycle. While the majority of metabolite pools remains homeostatic, ~14% respond to cell cycle progression. In particular, sulfur metabolism is redirected during the G1-S transition, and glutathione levels periodically change over the cell cycle with a peak in late S phase. A lack of glutathione perturbs cell size by uncoupling cell growth and division through dysregulation of KefB, a K; +; /H; +; antiporter. Overall, we here describe the impact of the; C. crescentus; cell cycle progression on metabolism, and in turn relate glutathione and potassium homeostasis to timely cell division.