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Study on improving drug for hyperchoresterolemia directed by sterol biosynthesis in Morus alba cell cultures

Research Project

Project/Area Number 09672168
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionToho University

Principal Investigator

NOMURA Taro  Toho University Faculty of Phrmaceutical Science Professor, 薬学部, 教授 (90057505)

Co-Investigator(Kenkyū-buntansha) KURODA Jun  Toho University Faculty of Phrmaceutical Science Assistant, 薬学部, 助手 (70287548)
HANO Yoshio  Toho University Faculty of Phrmaceutical Science Associate Professor, 薬学部, 助教授 (00156382)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsMorus alba / Morus bombycis / Callus cultures / Isoprenylated phenol / Isoprene biosynthesis / Fatty acid / β-oxidation / Tricarboxylic acid cycle / Inhibitor to biosynthesis / β-酸化 / 組織培養 / インプレン生合成 / インプレニルフェノール / クワカルス / イソプレノイド生合成 / HMG CoA還元酵素 / コンパクチン / β-シトステロール
Research Abstract

Morus alba cells and suspension cultures produce sterols and isoprenylated phenols in high yield. In the experiment with[2-ィイD113ィエD1C]acetate, comparison of incorporation of C-13 into polyketide moieties of isoprenylated phenols, kuwanons J, Q, R, and V, revealed that increasing of oxidation degrees decreased in corporation of C-13. This fact indicated that foremost biosynthesis of lesser hydroxylated compound, kuwanon V, followed by successive hydroxylation reactions to form kuwanon R and then kuwanon J. It was also suggested that chalco-moracin was biosynthesized from mulberrofuran E in the same way. There are two independent isoprene biosyntheses in M.alba cell cultures, one is sensitive to compactin (ML-236B), an inhibitor of HMG-CoA reductase, and the other is non-sensitive. In one of the two isoprene biosyntheses, non-sensitive to compactin, incorporated acetate was not intact acetate administered, but reconstructed acetate through tricarboxylic acid cycle (TCA cycle). To examine the participation of TCA cycle in the isoprene biosynthesis, fatty acid fraction was investigated. Palmitate was isolated from the callus cultures administered [2-ィイD113ィエD1C]acetate. The ィイD113ィエD1C-NMR spectrum of the palmitate demonstrated that the specified positions corresponding to the methyl group of the acetate were labeled with C-13. This fact suggested that the acetate from fatty acid through β-oxidation was incorporated into the isoprene unit via TCA cycle. This is the first example of contribution of fatty acid to the isoprene biosynthesis. It was thus indicated that fatty acid biosynthesis was also important factor in the development of improving drug for hyperchoresterolemia.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Yoshio Hano: "Dual p-Coumaroyl CoA Biosynthesis in Morus alba Cell Cultures"Heterocycles. 50・(2). 989-994 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Taro Nomura: "Studies on the Optically Active Diels-Alder Type Adducts from Mulberry Tree"Towards Natural Medicine Research in the 21st Century. 379-390 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 羽野芳生: "イソプレンの新しい生合成経路"ファルマシア. 34・(2). 142-146 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshio Hano: "Late Stage of Biosynthesis of Intermolecular Diels-Alder Type Adducts in Morus alba Cell Cultures"Heterocycles. 51・(2). 231-235 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Hano: "Late Stage of Biosynthesis of Intermolecular Diels-Alder Type adducts in Morus alba Cell Cultures"Heterocycles. 51(2). 231-235 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Hano: "Dual p-Coumaroyl CoA Biosynthesis in Morus alba Cell Cultures"Heterocycles. 50(2). 989-994 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Nomura: "Studies on the Optically Active Diels-Alder Type Adducts from Mulberry Tree"Towards Natural Medicine Research in the 21st Century. 379-390 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Hano: "New Route in an Isoprene Biosynthesis"Farmacia. 34(2). 142-146 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshio Hano: "Dual p-Coumaroyl CoA Biosynthesis in Morus alba Cell Cultures"Heterocycles. 50・(2). 989-994 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Taro Nomura: "Studies on the Optically Active Diels-Alder Type Adducts from Mulberry Tree"Towards Natural Medicine Research in the 21st Centuy. 379-390 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 羽野 芳生: "イソプレンの新しい生合成経路"ファルマシア. 34・(2). 142-146 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshio Hano: "Late Stage of Biosynthesis of Intcrmolecular Diels-Alder type Adducts in Monus alba Cell Cultures" Heterocycles. 51・(2). 231-235 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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