SignificanceBifunctional enzymes are widely distributed throughout bacteria and are involved in modulating bacterial phenotypes; however, regulatory mechanisms that control the activities of the opposing output domains have remained elusive. Studies on DcpG demonstrate that binding of ligands to the sensor globin domain differentially affect GGDEF and EAL domain activities and highlight a role for protein conformational changes in modulating enzymatic activity. Unusual sensor globin domain characteristics, including heme midpoint potentials, are likely important for the unique regulatory properties of DcpG. AsPaenibacillus dendritiformisresponds to changes in the gaseous environment by modulating biofilm formation, DcpG is likely important in modulating physiological responses to changes in O₂and NO levels, identifying a role for heme sensor signaling in the bacterium.