IdeR, a DtxR Family Iron Response Regulator, Controls Iron Homeostasis, Morphological Differentiation, Secondary Metabolism, and the Oxidative Stress Response in Streptomyces avermitilis.

Iron, an essential element for microorganisms, functions as a vital cofactor in a wide variety of key metabolic processes. On the other hand, excess iron may have toxic effects on bacteria by catalyzing the formation of reactive oxygen species through the Fenton reaction. The prevention of iron toxicity requires the precise control of intracellular iron levels in bacteria. Mechanisms of iron homeostasis in the genus (the producers of various antibiotics) are poorly understood. is the industrial producer of avermectins, which are potent anthelmintic agents widely used in medicine, agriculture, and animal husbandry. We investigated the regulatory role of IdeR, a DtxR family regulator, in In the presence of iron, IdeR binds to a specific palindromic consensus sequence in promoters and regulates 14 targets involved in iron metabolism (e.g., iron acquisition, iron storage, heme metabolism, and Fe-S assembly). IdeR also directly regulates 12 targets involved in other biological processes, including morphological differentiation, secondary metabolism, carbohydrate metabolism, and the tricarboxylic acid (TCA) cycle. transcription is positively regulated by the peroxide-sensing transcriptional regulator OxyR. A newly constructed deletion mutant (DideR) was found to be less responsive to iron levels and more sensitive to HO treatment than the wild-type strain, indicating that is essential for oxidative stress responses. Our findings, taken together, demonstrate that IdeR plays a pleiotropic role in the overall coordination of metabolism in spp. in response to iron levels. Iron is essential to almost all organisms, but in the presence of oxygen, iron is both poorly available and potentially toxic. species are predominantly present in soil where the environment is complex and fluctuating. So far, the mechanism of iron homeostasis in spp. remains to be elucidated. Here, we characterized the regulatory role of IdeR in the avermectin-producing organism IdeR maintains intracellular iron levels by regulating genes involved in iron absorption and storage. IdeR also directly regulates morphological differentiation, secondary metabolism, and central metabolism. is under the positive control of OxyR and is indispensable for an efficient response to oxidative stress. This investigation uncovered that IdeR acts as a global regulator coordinating iron homeostasis, morphological differentiation, secondary metabolism, and oxidative stress response in species. Elucidation of the pleiotropic regulation function of IdeR provides new insights into the mechanisms of how spp. adapt to the complex environment.