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Production of vitamin D hydroxylated compounds

Research Project

Project/Area Number 15K18686
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied biochemistry
Research InstitutionToyama Prefectural University

Principal Investigator

Yasuda kaori  富山県立大学, 工学部, 助教 (70707231)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsビタミンD水酸化体 / シトクロムP450 / 骨粗鬆症 / P450 / 骨粗鬆症治療薬
Outline of Final Research Achievements

There are lots of vitamin D hydroxylated compounds, and some of them are useful as medical drugs or authentic standard. In this study, we aimed to provide some vitamin D hydroxylated compounds such as active form of vitamin D2 by bioconversion process. We have reported the production of active form of vitamin D3 using the actinomycete CYP105A1 double variant, R73A/R84A. In this study, we found the new triple variant R73A/R84A/M239A to produce active form of vitamin D2. We also clarified that R73A/R84A was useful for the production of 25,26-dihydroxyvitamin D2, which is one of the vitamin D2 metabolite in the human body.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (25 results)

All 2017 2016 2015

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Production of an active form of vitamin D2 by genetically engineered CYP105A1.2017

    • Author(s)
      K. Yasuda K, Y. Yogo , H.Sugimoto, H. Mano, T. Takita, M. Ohta, M. Kamakura, S. Ikushiro, K. Yasukawa, Y. Shiro, T. Sakaki.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 486 Issue: 2 Pages: 336-341

    • DOI

      10.1016/j.bbrc.2017.03.040

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel screening system for high-affinity ligand of heredity vitamin D-resistant rickets-associated vitamin D receptor mutant R274L using bioluminescent sensor.2017

    • Author(s)
      H Mano M Nishikawa K Yasuda S Ikushiro N Saito D Sawada S Honzawa M Takano A Kittaka T Sakaki
    • Journal Title

      J Steroid Biochem Mol Biol.

      Volume: 167 Pages: 61-66

    • DOI

      10.1016/j.jsbmb.2016.11.008

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential hydroxylation of vitamin D2 by a genetically engineered CYP105A1.2016

    • Author(s)
      K. Hayashi, K. Yasuda, Y. Yogo, T. Takita, K. Yasukawa, M. Ohta, M. Kamakura, S. Ikushiro, T. Sakaki
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 473 Issue: 4 Pages: 853-858

    • DOI

      10.1016/j.bbrc.2016.03.139

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synthesis of the CYP24A1 major metabolite of 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3.2016

    • Author(s)
      Takano M, Yasuda K, Tohyama E, Higuchi E, Sakaki T, Kittaka A
    • Journal Title

      J. Steroid Biochem. Mol. Biol.

      Volume: - Pages: 75-78

    • DOI

      10.1016/j.jsbmb.2016.11.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Synthesis, metabolism, and biological activity of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D32016

    • Author(s)
      Masashi Takano, Kaori Yasuda, Erika Higuchi, Eri Tohyama, Akiko Takeuchi, Toshiyuki Sakaki, and Atsushi Kittaka
    • Journal Title

      J. Steroid Biochem. Mol. Biol.

      Volume: in press Pages: 30029-7

    • DOI

      10.1016/j.jsbmb.2015.07.016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Biological evaluation of double point modified analogues of 1,25-dihydroxy vitamin D2 as potential anti-leukemic agents2015

    • Author(s)
      Aoife Corcoran, Sharmin Nadkarni, Kaori Yasuda, Toshiyuki Sakaki, Geoffrey Brown, Andrzej Kutner , Ewa Marcinkowska
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 17 Issue: 2 Pages: 91-91

    • DOI

      10.3390/ijms17020091

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human hepatic metabolism of the anti-osteoporosis drug eldecalcitol involves sterol C4-methyl oxidase.2015

    • Author(s)
      K. Yasuda, Y. Iwanaga, K. Ogawa, H. Mano, S. Ueno, S. Kimoto, M. Ohta, M. Kamakura, S. Ikushiro and T. Sakaki
    • Journal Title

      Pharmacol. Res. Perspectives

      Volume: 3 Issue: 2

    • DOI

      10.1002/prp2.120

    • NAID

      110010000887

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of novel bioluminescent sensor to detect and discriminate between vitamin D receptor agonists and antagonists in living cells2015

    • Author(s)
      Hiroki Mano, Miyu Nishikawa, Kaori Yasuda, Shinichi Ikushiro, Nozomi Saito, Masashi Takano, Atsushi Kittaka, and Toshiyuki Sakaki
    • Journal Title

      Bioconjugate Chemistry

      Volume: 26 Issue: 10 Pages: 2038-2045

    • DOI

      10.1021/acs.bioconjchem.5b00433

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 骨粗鬆症治療薬ED-71の代謝にSC4MOLが関与する2015

    • Author(s)
      安田佳織, 岩永由麻, 小川和亮, 真野寛生, 上野千来, 木本周太朗, 太田美穂, 鎌倉昌樹, 生城真一, 榊利之
    • Journal Title

      ビタミン学会誌

      Volume: 89 Pages: 492-494

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] (24S)-2α-[2-(テトラゾール-2-イル)エチル]-1α,24,25-トリヒドロキシビタミンD3の合成.2017

    • Author(s)
      高野真史、安田佳織、真野寛生、遠山枝李、榊利之、橘高敦史
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] アゾール基を有するビタミンD誘導体のCYP24A1による代謝2017

    • Author(s)
      遠山枝李、安田佳織、真野寛生、鎌倉昌樹、生城真一、高野真史、橘高敦史、太田美穂、榊利之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 強い骨密度上昇作用を有するビタミンD誘導体の代謝様式の解明2016

    • Author(s)
      遠山枝李、安田佳織、生城真一、鎌倉昌樹、高野真史、橘高敦史、榊利之
    • Organizer
      日本薬物動態学会第30回年会(2016.10.13-15. 松本)
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 骨粗鬆症あるいは癌治療薬への応用を目指したビタミンD誘導体の代謝様式の解明2016

    • Author(s)
      遠山枝李、安田佳織、真野寛生、鎌倉昌樹、生城真一、太田美穂、高野真史、橘高敦史、榊利之  (2016.9.25-27. 仙台)
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Production of an active form of vitamin D and drug metabolites by recombinant actinomycete expressing genetically engineered CYP105A1.2016

    • Author(s)
      Yasuda K, Yogo Y, Takita T, Sugimoto H, Shiro Y, Mano H., Hayashi K, Kamakura M, Ohta M, lkushiro S, Yasukawa K, Sakaki T
    • Organizer
      The Fifth International Conference on Cofactors and Active Enzyme Molecule 2016
    • Place of Presentation
      Toyama
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Protein engineering of actinomycete CYP105A1 to produce active forms of vitamin D and drug metabolites2016

    • Author(s)
      Yasuda K, Yogo Y, Takita T, Sugimoto H, Shiro Y, Mano H, Hayashi K, Kamakura M, Ohta M, lkushiro S, Yasukawa K, Sakaki T
    • Organizer
      Cytochrome P450 Biodiversity & Biotechnology 2016
    • Place of Presentation
      Vancouver
    • Year and Date
      2016-07-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 分割型ルシフェラーゼを用いたビタミンD受容体リガンド検出バイオセンサーの応用.2016

    • Author(s)
      真野寛生、西川美宇、安田佳織、生城真一、高野真史、榊利之
    • Organizer
      日本ビタミン学会68回大会
    • Place of Presentation
      富山
    • Year and Date
      2016-06-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 強い骨密度上昇作用を有するビタミンD誘導体の代謝様式の解明.2016

    • Author(s)
      遠山枝李、安田佳織、生城真一、鎌倉昌樹、高野真史、橘高敦史、榊利之
    • Organizer
      日本ビタミン学会68回大会
    • Place of Presentation
      富山
    • Year and Date
      2016-06-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] CYP105A1の構造機能解析およびビタミンD水酸化体・医薬品代謝物の生産への応用2015

    • Author(s)
      余語祐哉、安田佳織、滝田禎亮、杉本宏、城宜嗣、真野寛生、林恵子、鎌倉昌樹、太田美穂、生城真一、保川清、榊利之
    • Organizer
      第88回 日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] SC4MOL, CYP3A4およびCYP24A1による骨粗鬆症治療薬エルデカルシトールの代謝2015

    • Author(s)
      安田佳織、岩永由麻、小川和亮、真野寛生、 太田美穂、鎌倉昌樹、生城真一、榊利之
    • Organizer
      日本薬物動態学会 第30年会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] 活性型ビタミンDや医薬品代謝物を生産する放線菌Streptmyces griseolus 由来CYP105A1の機能解析2015

    • Author(s)
      余語祐哉、安田佳織、滝田禎亮、杉本宏、城宜嗣、真野寛生、林恵子、鎌倉昌樹、太田美穂、生城真一、保川清、榊利之
    • Organizer
      第8回北陸合同バイオシンポジウム
    • Place of Presentation
      石川
    • Year and Date
      2015-10-30
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト由来メチルステロール酸化酵素SC4MOLによるビタミンD誘導体の代謝2015

    • Author(s)
      安田佳織、岩永由麻、小川和亮、高野真史、 橘高敦史、太田美穂、鎌倉昌樹、生城真一、榊利之
    • Organizer
      第1回ネオビタミンDワークショップ
    • Place of Presentation
      大津
    • Year and Date
      2015-08-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 活性型ビタミンDや医薬品代謝物を生産するCYP105A1の機能解析2015

    • Author(s)
      余語祐哉、安田佳織、滝田禎亮、杉本宏、城宜嗣、真野寛生、林恵子、鎌倉昌樹、太田美穂、生城真一、保川清、榊利之
    • Organizer
      日本農芸化学会中部・関西合同支部会
    • Place of Presentation
      富山
    • Year and Date
      2015-08-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Sterol C4-methyl oxidase plays an important role in the hepatic metabolism of the anti-osteoporosis drug eldecalcitol2015

    • Author(s)
      Yasuda K, Ogawa K, Iwanaga Y, Mano H, Takano M, Kittaka A, Ohta M, Ikushiro S, Sakaki T
    • Organizer
      Metals in Biology
    • Place of Presentation
      和光
    • Year and Date
      2015-06-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Protein engineering of CYP105A1 to produce active forms of vitamin D and drug metabolites2015

    • Author(s)
      Yuya Yogo, Kaori Yasuda, Teisuke Takita, Hiroshi Sugimoto, Yoshitsugu Shiro, Hiroki Mano, Keiko Hayashi, Masaki Kamakura, Miho Ohta, Shinichi lkushiro, Kiyoshi Yasukawa,
    • Organizer
      The 19th International Conference on Cytochrome P450
    • Place of Presentation
      東京
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 放線菌由来CYP105A1変異体を用いたビタミンD水酸化体および医薬品代謝物の生産.2015

    • Author(s)
      安田佳織、余語祐哉、滝田禎亮、保川清、杉本宏、城宜嗣、真野寛生、太田美穂、生城真一、榊利之
    • Organizer
      日本ビタミン学会67回大会
    • Place of Presentation
      奈良
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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