title: Nitrogen oxide cycle regulates nitric oxide levels and bacterial cell signaling.
abstract: 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.
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Oguchi
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kusama
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sugiura
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Moriya
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Yuriya
authors.initials: Y
authors.lastname: Yukioka
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takaya
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yajima
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Kanju
authors.initials: K
authors.lastname: Ohsawa
authors.affiliation: Laboratory of Microbial Engineering, Kitasato Institute for Life Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-855, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Life Science Research Center, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa 252-0880, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takano
authors.affiliation: Life Science Research Center, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa 252-0880, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shoun
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D015398:Signal Transduction; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D009566:Nitrates; D009573:Nitrites; D009589:Nitrogen Oxides; D009569:Nitric Oxide; D010105:Oxygenases; C114415:nitric oxide dioxygenase