础产蝉迟谤补肠迟:听 Changes of the nutrient environment have long聽been used to study regulation and聽adaptation phenomena in microorganisms聽and they remain a topic of active聽investigation in the modern era.聽While much is known about the molecular聽interactions governing the regulation聽of key metabolic processes in response to applied聽perturbations,聽they are insufficiently quantified for predictive bottom-up modeling.聽I will describe聽a top-down modeling approach, expanding the recently established coarse-grained聽proteome allocation models聽from steady-state growth into the kinetic regime.聽Using only qualitative聽knowledge of the underlying regulatory processes and imposing the聽condition of聽flux balance, we derive a quantitative model of bacterial growth transitions聽independent of inaccessible kinetic parameters. The resulting flux-controlled聽regulation聽model accurately predicts the time course of gene expression and聽biomass accumulation聽in response to carbon upshifts and downshifts (e.g.,聽diauxic shifts) without adjustable聽parameters. As predicted by the model and聽validated by quantitative proteomics, cells聽exhibit suboptimal recovery聽kinetics in response to nutrient shifts due to a rigid strategy of聽protein聽synthesis allocation, which is not directed towards alleviating specific聽metabolic聽bottlenecks. Our approach is independent of kinetic parameters and thus聽outlines a聽theoretical framework for describing a broad range of such kinetic processes聽without聽detailed knowledge of the underlying biochemical reactions.