A metabolic hierarchy directs cell cycle transition and morphogenesis

To optimize survival, cells must align differentiation and proliferation with metabolic status. Yet, how metabolic cues fine-tune cell cycle programs and morphogenesis remain unclear. Here, we show that cytosolic redox dynamics critically govern cell cycle transitions in Caulobacter crescentus . By integrating evolutionary genetics with fluxomics, we uncover temporally orchestrated shifts in core metabolic pathways that remodel cytosolic redox across the cell cycle. Early stages channel carbon flux toward unsaturated fatty-acid synthesis and a reverse-TCA to drive cytosolic oxidation-coupled G1-S transition. The later stages depend on an enhanced forward-TCA cycle that promote cytosolic reduction-driven proliferation. Strikingly, perturbing fatty-acid synthesis or reverse/forward-TCA uncouples growth from proliferation. Intriguingly, a biphasic glucose uptake program dictates the cell cycle-stage-specific metabolism. These findings reveal an unprecedented metabolic-redox circuitry coordinating morphogenesis with cell cycle progression in a carefully choreographed ménage à trois .