The facultative chemolithoautotroph Cupriavidus necator is capable of heterotrophic growth on diverse carbon sources or of autotrophic growth using CO2 fixation with H2 as an energy source. Under stress conditions, it is capable of producing biodegradable polyesters (polyhydroxyalkanoates, PHAs) as a storage material occupying a high proportion of the total biomass. This metabolic versatility means that C. necator is under intense study for sustainable biotechnology processes; however a relative lack of understanding of the overall regulatory architecture has limited its application. The major mechanisms by which proteins can respond to shifting cellular demands are protein expression change and/or allosteric regulation. Here we use two powerful proteomics methods to investigate these responses in C. necator cells grown on balanced and low nitrogen (PHA-inducing) media. Using quantitative proteomics and protein stability analysis (which can report on conformation change), we find that proteins across different pathways respond through one or both of these regulatory modes, including coordinated adaption to nutrient stress by the PHA pathway, the Calvin cycle, and ribosomal proteins.