Updated project metadata. Chemostat cultivation mode imposes selective pressure on cells, which may result slow adaptation in the physiological state over time. We applied a two-compartment scale-down chemostat system simulating glucose gradients to characterize the long-term (100’s of hours) response of S. cerevisiae to fluctuating glucose concentrations. A wild-type strain and a recombinant strain, expressing an insulin precursor, were cultured in the scale-down system, and analyzed at the physiological and proteomic level. Phenotypes of both strains were compared to those observed in a well-mixed single chemostat system.