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Heme transport and degradation by enteric pathogens

Research Project

Project/Area Number 17K05933
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bio-related chemistry
Research InstitutionYamaguchi University

Principal Investigator

Shin-ichi Ozaki  山口大学, 大学院創成科学研究科, 教授 (40280581)

Co-Investigator(Kenkyū-buntansha) 阿座上 弘行  山口大学, 大学院創成科学研究科, 教授 (40263850)
木股 洋子 (有賀洋子)  山口大学, 大学院創成科学研究科, 准教授 (60255429)
永野 真吾  鳥取大学, 工学研究科, 教授 (60286440)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsヘム / 鉄
Outline of Final Research Achievements

Some Gram-negative pathogens import host heme into the cytoplasm and utilize it as an iron source for their survival. We report here that HmuS, encoded by the heme utilizing system (hmu) locus in Y. pseudotuberculosis, cleaves the protoporphyrin ring to release iron from heme. A liquid chromatography/mass spectrometry analysis revealed that the degradation products of this reaction are two biliverdin isomers that result from transformation of a verdoheme intermediate. Although HmuS does not share amino acid sequence homology with heme oxygenase (HO), a well-known heme-degrading enzyme, absorption and resonance Raman spectral analyses suggest that the heme iron is coordinated with an axial histidine residue and a water molecule in both enzymes. The search for HmuS inhibitors is underway to prevent the proliferation of the enteric pathogenic bacteria.

Academic Significance and Societal Importance of the Research Achievements

様々な病気や細菌による感染リスクの高い高齢者が増える社会を迎え、病原性細菌の感染を抑えることは重要な課題である。本研究から得られる知見は、こうした細菌の生育を抑えることに寄与するものである。本研究により、グラム陰性病原性細菌であっても好気性細菌と通性嫌気性細菌ではヘムの菌内への取り込みやヘムからの鉄の抽出プロセスが異なることが明らかになってきた。細菌が持つ鉄獲得戦略の多様性と普遍性を精緻に検証することは学術的にも興味深い事項である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Synthesis of Glycosides of Resveratrol, Pinostilbene, and Piceatannol by Bioconversion with Phytolacca Americana2019

    • Author(s)
      Kei Shimoda, Naoji Kubota, Daisuke Uesugi, Yuya Fujitaka, Shouta Doi, Hiroki Hamada, Atsuhito Kuboki, Yuya Kiriake, Takafumi Iwaki, Tomohiro Saikawa, Shin-ichi Ozaki
    • Journal Title

      Natural Product Communications

      Volume: 14 Issue: 8 Pages: 1-3

    • DOI

      10.1177/1934578x19868396

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Application of Racemization Process to Dynamic Resolution of (RS)-Phenylephrine to (R)-Phenylephrine β-D-Glucoside by Nicotiana tabacum Glucosyltransferase2018

    • Author(s)
      Yuya Fujitakaa, Daisuke Uesugia, Hatsuyuki Hamadab, Hiroki Hamadaa,*, Kei Shimodac, Masayoshi Yanagia, Manami Inouea and Shin-ichi Ozaki
    • Journal Title

      Natural Product Communications

      Volume: 13 Pages: 1465-1466

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] HmuS from Yersinia pseudotuberculosis is a non-canonical heme-degrading enzyme to acquire iron from heme2017

    • Author(s)
      Onzuka, M., Sekine, Y., Uchida, T., Ishimori, K., and Ozaki, S.
    • Journal Title

      Biochimica et Biophysica Acta

      Volume: 印刷中 Issue: 7 Pages: 1870-1878

    • DOI

      10.1016/j.bbagen.2017.04.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 病原性細菌のヘム分解2019

    • Author(s)
      下村直道・沖本雄大・小崎紳一
    • Organizer
      錯体化学討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Heme transport and metabolism in pathogenic bacteria2018

    • Author(s)
      S. Ozaki *, M. Onzuka, N. Shimomura
    • Organizer
      International Conference on Coordination Chemistry
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 仮性結核菌のヘム代謝酵素の機能と構造2017

    • Author(s)
      恩塚 誠士 安川 諒 小崎 紳一
    • Organizer
      第17回 日本蛋白質科学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Functions of the heme degradation enzymes in Yersinia pseudotuberculosis2017

    • Author(s)
      Masato Onzuka, Daishi Miyakawa, Naomichi Shimomura, Shin-ichi Ozaki
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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