IdeR, a DtxR Family Iron Response Regulator, Controls Iron Homeostasis, Morphological Differentiation, Secondary Metabolism, and the Oxidative Stress Response in Streptomyces avermitilis
IdeR, a DtxR Family Iron Response Regulator, Controls Iron Homeostasis, Morphological Differentiation, Secondary Metabolism, and the Oxidative Stress Response in Streptomyces avermitilis
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IdeR 是一种 DtxR 家族铁反应调节剂，可控制阿维链霉菌中的铁稳态、形态分化、次级代谢和氧化应激反应
DOI：
10.1128/aem.01503-18
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发表时间：
2018-11-01
影响因子：
4.4
通讯作者：
Chen, Zhi
中科院分区：
文献类型：
--
作者：
Cheng, Yaqing;Yang, Renjun;Chen, Zhi
铁对几乎所有生物体都是必不可少的，但在氧气存在的情况下，铁既难以获得，又可能有毒。链霉菌主要存在于环境复杂多变的土壤中。到目前为止，链霉菌铁稳态的机制。仍有待阐明。在这里，我们的特点是在阿维菌素生产生物S的调节作用的IdeR。阿维菌素。IdeR通过调节参与铁吸收和储存的基因来维持细胞内铁水平。IdeR还直接调节形态分化、次生代谢和中心代谢。ideR受OxyR的正调控，对于有效应对氧化应激是必不可少的。本研究发现，IdeR作为一个全球性的调节器协调铁稳态，形态分化，次生代谢，氧化应激反应的链霉菌物种。阐明IdeR的多效性调节功能为链霉菌如何调节其代谢机制提供了新的见解。适应复杂的环境。摘要铁是微生物的必需元素，在多种关键代谢过程中作为重要的辅助因子发挥作用。另一方面，过量的铁可通过芬顿反应催化活性氧物质的形成而对细菌具有毒性作用。预防铁毒性需要精确控制细菌细胞内铁水平。链霉菌属（各种抗生素的生产者）的铁稳态机制知之甚少。阿维菌素是阿维菌素的工业生产者，阿维菌素是广泛应用于医药、农业和畜牧业的强效驱虫剂。我们研究了DtxR家族调节因子IdeR在S.阿维菌素。在铁的存在下，IdeR结合启动子中的特定回文共有序列，并调节14个参与铁代谢的靶点（例如，铁获取、铁储存、血红素代谢和Fe-S组装）。IdeR还直接调节其他生物过程中涉及的12个靶标，包括形态分化、次级代谢、碳水化合物代谢和三羧酸（TCA）循环。ideR转录受过氧化物敏感转录调节因子OxyR的正调控。一个新构建的ideR缺失突变体（DideR）被发现是较低的铁水平和更敏感的H2 O2处理比野生型菌株，表明ideR是必不可少的氧化应激反应。我们的研究结果表明，IdeR在链霉菌代谢的整体协调中起着多效性作用。对铁含量的反应。重要性铁对几乎所有生物体都是必不可少的，但在氧气存在的情况下，铁的可用性很差，而且可能有毒。链霉菌主要存在于环境复杂多变的土壤中。到目前为止，链霉菌铁稳态的机制。仍有待阐明。在这里，我们的特点是在阿维菌素生产生物S的调节作用的IdeR。阿维菌素。IdeR通过调节参与铁吸收和储存的基因来维持细胞内铁水平。IdeR还直接调节形态分化、次生代谢和中心代谢。ideR受OxyR的正调控，对于有效应对氧化应激是必不可少的。本研究发现，IdeR作为一个全球性的调节器协调铁稳态，形态分化，次生代谢，氧化应激反应的链霉菌物种。阐明IdeR的多效性调节功能为链霉菌如何调节其代谢机制提供了新的见解。适应复杂的环境。
Iron is essential to almost all organisms, but in the presence of oxygen, iron is both poorly available and potentially toxic. Streptomyces species are predominantly present in soil where the environment is complex and fluctuating. So far, the mechanism of iron homeostasis in Streptomyces spp. remains to be elucidated. Here, we characterized the regulatory role of IdeR in the avermectin-producing organism S. avermitilis. 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. ideR 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 Streptomyces species. Elucidation of the pleiotropic regulation function of IdeR provides new insights into the mechanisms of how Streptomyces spp. adapt to the complex environment. ABSTRACT 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 Streptomyces (the producers of various antibiotics) are poorly understood. Streptomyces avermitilis 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 S. avermitilis. 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. ideR transcription is positively regulated by the peroxide-sensing transcriptional regulator OxyR. A newly constructed ideR deletion mutant (DideR) was found to be less responsive to iron levels and more sensitive to H2O2 treatment than the wild-type strain, indicating that ideR is essential for oxidative stress responses. Our findings, taken together, demonstrate that IdeR plays a pleiotropic role in the overall coordination of metabolism in Streptomyces spp. in response to iron levels. IMPORTANCE Iron is essential to almost all organisms, but in the presence of oxygen, iron is both poorly available and potentially toxic. Streptomyces species are predominantly present in soil where the environment is complex and fluctuating. So far, the mechanism of iron homeostasis in Streptomyces spp. remains to be elucidated. Here, we characterized the regulatory role of IdeR in the avermectin-producing organism S. avermitilis. 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. ideR 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 Streptomyces species. Elucidation of the pleiotropic regulation function of IdeR provides new insights into the mechanisms of how Streptomyces spp. adapt to the complex environment.