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Whole cell-dependent production of polyphenol conjugates using genetically engineered budding yeast

Research Project

Project/Area Number 23580179
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Food science
Research InstitutionToyama Prefectural University

Principal Investigator

IKUSHIRO Shinichi  富山県立大学, 工学部, 准教授 (50244679)

Co-Investigator(Kenkyū-buntansha) SAKAKI Toshiyuki  富山県立大学, 工学部, 教授 (70293909)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords機能性成分 / ポリフェノール / グルクロン酸抱合 / 硫酸抱合 / UDP-グルクロン酸転移酵素 / 硫酸基転移酵素 / 国際情報交換、フィンランド / 国際情報交流、フィンランド
Research Abstract

In order to synthesize the conjugates as dietary metabolites, polyphenols, we have developed several mammalian UDP-glucuronosyltransferases (UGT) or sulfotransferase (SULT) expression systems in budding yeast. For the glucuronide production, mammalian UGT and UDP-glucose dehydrogenase (UGDH) were expressed in budding yeas using a multicopy and a genome integrated vectors. Using genetically engineered yeast containing UGT and UGDH, glucuronide formation of quercetin was examined. Querectin with multiple glucuronidating sites was conjugated as isoform-dependent formation using UGT isoforms. In the presence of glucose and ammonium sulfate, formation of sulfated quercetin was observed in whole-cell production system with SULT isoforms .These expression system of mammalian UGT or SULT in budding yeast would be a powerful tool for enzyme-assisted synthesis of various dietary metabolites including glucuronides and sulfates.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (47 results)

All 2013 2012 2011 Other

All Journal Article (20 results) (of which Peer Reviewed: 14 results) Presentation (23 results) (of which Invited: 1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Comparison of Serotonin Glucuronidation Activity of UDP- glucuronosyltransferase 1a6a (Ugt1a6a) and Ugt1a6b : Evidence for the Preferential Expression of Ugt1a6a in the Mouse2013

    • Author(s)
      Uchihashi S, Nishikawa M., Sakaki T., and Ikushiro S.
    • Journal Title

      Brain Drug Metab Pharmacokinet

      Volume: 28 Pages: 260-264

    • Related Report
      2013 Final Research Report
  • [Journal Article] UV-dependent production of 25-hydroxyvitamin D2 in the recombinant yeast cells expressing human CYP2R12013

    • Author(s)
      Yasuda K, Endo M, Ikushiro S,Kamakura M, Ohta M, Sakaki T.
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 434 Pages: 311-315

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] Comparison of Serotonin Glucuronidation Activity of UDP-glucuronosyltransferase 1a6a (Ugt1a6a) and Ugt1a6b: Evidence for the Preferential Expression of Ugt1a6a in the Mouse Brain2013

    • Author(s)
      Uchihashi S, Nishikawa M., Sakaki T., and Ikushiro S.
    • Journal Title

      Drug Metab Pharmacokinet.

      Volume: 28 Pages: 260-264

    • NAID

      130004463298

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Possible Mechanism for 2,3',4,4',5'-Pentachlorobiphenyl-Mediated Decrease in Serum Thyroxine Level in Mice2013

    • Author(s)
      Kato Y, Onishi M, Haraguchi K, Ikushiro S, Ohta C, Koga N, Endo T, Yamada S, and Degawa M
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 36 Pages: 1594-1601

    • NAID

      130003361538

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Avian Cytochrome P450 (CYP) 1-3 Family Genes : Isoforms, Evolutionary Relationships, and mRNA Expression in Chicken Liver2013

    • Author(s)
      Kensuke P WATANABE, et al.
    • Journal Title

      PLoS ONE

      Volume: 8(9) Issue: 9 Pages: e75689-e75689

    • DOI

      10.1371/journal.pone.0075689

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The critical role of amino acid residue at position 117 of mouse UDP- glucuronosyltransfererase 1a6a and 1a6b in resveratrol glucuronidation2012

    • Author(s)
      Uchihashi S, Nishikawa M., Sakaki T., and Ikushiro S.
    • Journal Title

      J.Biochem

      Volume: 152 Pages: 331-340

    • NAID

      10031166146

    • Related Report
      2013 Final Research Report
  • [Journal Article] Human UGT expression in insect cells; the ratio of active to inactive recombinant proteins and the effects of a C-terminal His-tag on glucuronidation kinetics2012

    • Author(s)
      Zhang H., Patana A., Mackenzie PI., Ikushiro S., Goldman A., and Finel M.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 40 Pages: 1935-1944

    • Related Report
      2013 Final Research Report
  • [Journal Article] The effects of N-glycosylation on the glucuronidation of zidovudine and morphine by UGT2B7 expressed in HEK293 cells2012

    • Author(s)
      Nagaoka K, Hanioka N, Ikushiro S, Yamano S, Narimatsu S.
    • Journal Title

      Drug Metab Pharmacokinet.

      Volume: 27 Pages: 388-397

    • NAID

      130004463270

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The critical role of amino acid residue at position 117 of mouse UDP-glucuronosyltransfererase 1a6a and 1a6b in resveratrol glucuronidation.2012

    • Author(s)
      Uchihashi S, Nishikawa M., Sakaki T., and Ikushiro S.
    • Journal Title

      J.Biochem.

      Volume: 152 Pages: 331-340

    • NAID

      10031166146

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human UGT expression in insect cells; the ratio of active to inactive recombinant proteins and the effects of a C-terminal His-tag on glucuronidation kinetics.2012

    • Author(s)
      Zhang H., Patana A., Mackenzie PI., Ikushiro S., Goldman A., and Finel M.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 40 Pages: 1935-1944

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparative Study on 2,2',4,5,5'-Pentachlorobiphenyl-Mediated Decrease in Serum Thyroxine Level between C57BL/6 and Its Transthyretin-Deficient Mice.2012

    • Author(s)
      Kato Y., Tamaki S., Haraguchi K.,Ikushiro S., Sekimoto M., Ohta C., Endo T., Koga N., Yamada S., and Degawa M.
    • Journal Title

      Toxicology and Applied Pharmacology

      Volume: 263 Pages: 323-329

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human cytochrome P450-dependent differential metabolism among three 2α-substituted-1α,25-dihydroxyvitamin D(3) analogs.2012

    • Author(s)
      Yasuda K, Ikushiro S, Kamakura M, Takano M, Saito N, Kittaka A, Chen TC, Ohta M, Sakaki T.
    • Journal Title

      J Steroid Biochem Mol Biol

      Volume: 133 Pages: 84-92

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple isoform dependent glucuronidation of a selective c-Fos/activator protein-1 inhibitor T-52242011

    • Author(s)
      Uchihashi, S.,Fukumoto, H., Onoda, M., Hayakawa, H., Ikushiro, S., and Sakaki, T.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 39 Pages: 803-813

    • Related Report
      2013 Final Research Report
  • [Journal Article] Sequential metabolism of sesamine by cytochrome P450 and UGT-glucuronosyltransferase in human liver2011

    • Author(s)
      Yasuda K, Ikushiro S, Kamakura M, Munetsuna E, Ohta M, Sakaki T.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 39 Pages: 1538-1545

    • Related Report
      2013 Final Research Report
  • [Journal Article] Multiple isoform dependent glucuronidation of a selective c-Fos/activator protein-1 inhibitor T-5224.2011

    • Author(s)
      Uchihashi, S.,Fukumoto, H., Onoda, M., Hayakawa, H., Ikushiro, S., and Sakaki, T.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 39 Pages: 803-813

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Possible Mechanism for 2,2',4,4',5,5'-Hexachlorobiphenyl- Mediated Decrease in Serum Thyroxine Level in Mice.2011

    • Author(s)
      Kato, Y., Onishi, M., Haraguchi, K., Ikushiro, S., Ota, C., Koga, N., Endo, T., Yamada, S., and Degawa, M.
    • Journal Title

      Toxicology and Applied Pharmacology

      Volume: 254 Pages: 48-55

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The impact of pharmacogenetics of metabolic enzymes and transporters on the pharmacokinetics of telmisartan in healthy volunteers2011

    • Author(s)
      Yamada, A., Maeda, K., Ishiguro, N., Tsuda, Y., Igarashi, T., Ebner, T., Roth, W., Ikushiro, S., and Sugiyama, Y.
    • Journal Title

      Pharmacogenetics and Genomics

      Volume: 21 Pages: 523-530

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sequential metabolism of sesamine by cytochrome P450 and UGT-glucuronosyltransferase in human liver.2011

    • Author(s)
      Yasuda K, Ikushiro S, Kamakura M, Munetsuna E, Ohta M, Sakaki T.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 39 Pages: 1538-1545

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] UDP-Glucuronosyltransferase 2B15 Polymorphism on Bisphenol A Glucuronidation.2011

    • Author(s)
      Hanioka, N., Hiroyuki, Oka, H., Nagaoka, K., Ikushiro, S., Narimatsu, S.
    • Journal Title

      Archives of Toxicology

      Volume: 85 Pages: 1378-1381

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of Bucolome N-Glucuronide Formation: Organ specificity and Identification of Rat UDP-Glucuronosyltransferase Isoform(s).2011

    • Author(s)
      Kanoh, H., Tada,M., Ikushiro, S., and Mohri, K.
    • Journal Title

      Pharmacology & Pharmacy

      Volume: 2 Pages: 151-158

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 異物抱合酵素発現酵母を用いたフラボノイド抱合体の調製2013

    • Author(s)
      生城真一、長谷川嵩、黒田将司、西川美宇、鎌倉昌樹、榊利之
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] Whole cell-dependent production of polyphenol conjugates using genetically engineered budding yeast2013

    • Author(s)
      S. Ikushiro, M. Nishikawa, T. Sakaki
    • Organizer
      第6回国際ポリフェノール学会
    • Place of Presentation
      ブエノスアイレス
    • Related Report
      2013 Final Research Report
  • [Presentation] ラットを用いたセサミンと医薬品の相互作用の解析2013

    • Author(s)
      上野千来、安田佳織、西川美宇、生城真一、鎌倉昌樹、榊利之
    • Organizer
      第18回日本フードファクター学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 異物代謝酵素発現酵母を用いたポリフェノール抱合代謝物の調製2013

    • Author(s)
      生城真一、小路征、西川美宇、鎌倉昌樹、榊利之
    • Organizer
      日本ビタミン学会第65回
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] セサミンと医薬品の相互作用2013

    • Author(s)
      上野千来、安田佳織、西川美宇、生城真一、鎌倉昌樹、榊利之
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 薬物代謝酵素発現酵母を用いたヒト医薬品代謝物調製2013

    • Author(s)
      西川美宇 、増山優香、安田佳織、小路征 、鎌倉昌樹、生城真一、榊利之
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Whole cell-dependent production of polyphenol conjugates using genetically engineered budding yeast2013

    • Author(s)
      S. Ikushiro, M. Nishikawa, T. Sakaki
    • Organizer
      第6回国際ポリフェノール学会
    • Place of Presentation
      ブエノスアイレス
    • Related Report
      2013 Annual Research Report
  • [Presentation] 遺伝子改変出芽酵母を用いた食品成分代謝物調製技術の開発2012

    • Author(s)
      生城真一、西川美宇、増山優香、鎌倉昌樹、榊利之
    • Organizer
      第17回日本フードファクター学会
    • Place of Presentation
      静岡
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 出芽酵母発現系を用いた医薬品・食品代謝物調製技術の確立2012

    • Author(s)
      西川美宇、生城真一、長谷川嵩、榊利之
    • Organizer
      日本ビタミン学会第64回大会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
  • [Presentation] 異物代謝酵素発現酵母株を用いた医薬品・食品代謝物調製技術の開発2012

    • Author(s)
      生城真一
    • Organizer
      2012年度 酵素補酵素研究会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Construction of sequential drug metabolizing system by CYP and UGT using genetically engineered yeast.2012

    • Author(s)
      Miyu Nishikawa, Yuuka Masuyama, Kaori Yasuda, Takashi Hasegawa, Masaki Kamakura, Toshiyuki Sakaki and Shinichi Ikushiro
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Whole cell-dependent production of drug metabolites using genetically engineered budding2012

    • Author(s)
      Shinichi Ikushiro, Miyu Nishikawa, and Toshiyuki Sakaki
    • Organizer
      P450発見50周年記念シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 薬物代謝酵素発現酵母株を用いた医薬品代謝物調製技術の開発2012

    • Author(s)
      西川 美宇、増山 優香、長谷川 嵩、鎌倉 昌樹、榊 利之、生城 真一
    • Organizer
      2012年度農芸化学会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] 哺乳動物由来UDP-グルクロン酸転移酵素発現出芽酵母を用いた抱合体産生2012

    • Author(s)
      長谷川 嵩、西川 美宇、生城 真一、榊 利之
    • Organizer
      2012年度農芸化学会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] ヒト由来硫酸基転移酵素発現出芽酵母を用いた抱合体産生2012

    • Author(s)
      生城 真一、布目 基倫、西川 美宇、榊 利之
    • Organizer
      2012年度農芸化学会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] 出芽酵母発現系を用いた硫酸抱合体調製技術の開発2011

    • Author(s)
      生城真一、西川美宇、布目基倫、増山優香、鎌倉昌樹、榊利之
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Whole cell-dependent production of dietary conjugated metabolites using genetically engineered budding yeast ICoFF20112011

    • Author(s)
      Shinichi Ikushiro, Miyu Nishikawa, Yuuka Masuyama, Masaki Kamakura, and Toshiyuki Sakaki
    • Organizer
      第5回食品因子国際会議
    • Place of Presentation
      台北
    • Related Report
      2013 Final Research Report
  • [Presentation] Production of Glucurono- or Sulfo-conjugated Metabolites Using Genetically Engineered Yeast Expressing CYP with UGT or SULT2011

    • Author(s)
      Toshiyuki Sakaki, Yuuka Masuyama, Motomichi Nunome, Yumi Takano, Kaori Yasuda, Masaki Kamakura, and Shinichi Ikushiro
    • Organizer
      17thInternational Conference on Cytochrome P450(招待講演)
    • Place of Presentation
      Manchester, UK
    • Related Report
      2011 Research-status Report
  • [Presentation] グルクロン酸抱合酵素系発現酵母を用いた抱合体合成2011

    • Author(s)
      西川美宇、増山優香、長谷川嵩、鎌倉昌樹、榊利之、生城真一
    • Organizer
      第84回 日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] 出芽酵母発現系を用いた硫酸抱合体調製技術の開発2011

    • Author(s)
      生城真一、西川美宇、布目基倫、増山優香、鎌倉昌樹、榊利之
    • Organizer
      第84回 日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] Whole cell-dependent production of acyl glucuronide using genetically engineered budding yeast2011

    • Author(s)
      Miyu Nishikawa, Yuuka Masuyama, Takashi Hasegawa,Masaki Kamakura, Toshiyuki Sakaki, and Shinichi Ikushiro
    • Organizer
      JSSX2011(日本薬物動態学会)
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] Preparation of sulfates using genetically engineered budding yeast2011

    • Author(s)
      Shinichi Ikushiro, Miyu Nishikawa, Motomichi Nunome, Yuuka Masuyama, Masaki Kamakura, and Toshiyuki Sakaki
    • Organizer
      JSSX2011(日本薬物動態学会)
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] Whole cell-dependent production of dietary conjugated metabolites using genetically engineered budding yeast2011

    • Author(s)
      Shinichi Ikushiro, Miyu Nishikawa, Yuuka Masuyama, Masaki Kamakura, and Toshiyuki Sakaki
    • Organizer
      ICoFF2011(第5回食品因子国際会議)
    • Place of Presentation
      台北、台湾
    • Related Report
      2011 Research-status Report
  • [Remarks] ホームページ:

    • URL

      http://www.pu-toyama.ac.jp/BR/sakaki/

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.pu-toyama.ac.jp/BR/sakaki/

    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] 出芽酵母形質転換体2013

    • Inventor(s)
      生城真一、榊利之、安田佳織
    • Industrial Property Rights Holder
      富山県
    • Industrial Property Rights Type
      特許
    • Acquisition Date
      2013-03-13
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 出芽酵母形質転換体2012

    • Inventor(s)
      生城真一、榊利之、安田佳織
    • Industrial Property Rights Holder
      富山県
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-07-12
    • Acquisition Date
      2013-03-01
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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