Journal Article Nitrogen oxide cycle regulates nitric oxide levels and bacterial cell signaling

Sasaki, Yasuyuki  ,  Oguchi, Haruka  ,  Kobayashi, Takuya  ,  Kusama, Shinichiro  ,  Sugiura, Ryo  ,  Moriya, Kenta  ,  Hirata, Takuya  ,  Yukioka, Yuriya  ,  Takaya, Naoki  ,  Yajima, Shunsuke  ,  Ito, Shinsaku  ,  Okada, Kiyoshi  ,  Ohsawa, Kanju  ,  Ikeda, Haruo  ,  Takano, Hideaki  ,  Ueda, Kenji  ,  Shoun, Hirofumi

6p.22038 , 2016-02 , Nature Publishing Group
Nitric oxide (NO) signaling controls various metabolic pathways in bacteria and higher eukaryotes. Cellular enzymes synthesize and detoxify NO; however, a mechanism that controls its cellular homeostasis has not been identified. Here, we found a nitrogen oxide cycle involving nitrate reductase (Nar) and the NO dioxygenase flavohemoglobin (Fhb), that facilitate inter-conversion of nitrate, nitrite, and NO in the actinobacterium Streptomyces coelicolor. This cycle regulates cellular NO levels, bacterial antibiotic production, and morphological differentiation. NO down-regulates Nar and up-regulates Fhb gene expression via the NO-dependent transcriptional factors DevSR and NsrR, respectively, which are involved in the auto-regulation mechanism of intracellular NO levels. Nitrite generated by the NO cycles induces gene expression in neighboring cells, indicating an additional role of the cycle as a producer of a transmittable inter-cellular communication molecule.

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