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 remain 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 effects of the C. crescentus cell cycle progression on metabolism, and in turn relate glutathione and potassium homeostasis to timely cell division. Hartl et al. demonstrate how metabolism and the cell cycle are coupled in prokaryotic cells by analysing the metabolome during the cell cycle in Caulobacter crescentus. Whereas the levels of most metabolites are independent of the cell cycle, glutathione fluctuates and is required for coordinated cell cycle progression.