We investigated variations in cell growth and ATP Sulfurylase (ATPS) activity when two cyanobacterial strains—Synechocystis sp. PCC6803 and Synechococcus sp. WH7803—were grown in conventional media, and media with low ammonium, low sulfate and a high CO2/low O2 atmosphere. In both organisms, a transition and adaptation to the reconstructed environmental media resulted in a decrease in ATPS activity. This variation appears to be decoupled from growth rate, suggesting the enzyme is not rate-limiting in S assimilation and raising questions about the role of ATPS redox regulation in cell physiology and throughout Earth history.