Search for inhibitors of NADH-fumarate reductase from second metabolites of bacteria, actinomycetes and fungi

• Project/Area Number: 21780115
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: Kitasato University
• Principal Investigator: MORI Mihoko Kitasato University, 大学院・感染制御科学府, 助教 (20425648)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 生物活性物質 / 寄生虫 / 感染症 / 機器分析 / 精製 / ミトコンドリア電子伝達系 / NADH-フマル酸還元酵素 / 二次代謝産物 / 微生物 / 糸状菌 / 放線菌 / 微生物二次代謝産物

Research Abstract

Screening for inhibitors of NADH-fumarate reductase was conducted using about 8,200 samples of cultured broths of fungi, actinomycetes and bacteria. About 2% of the broths inhibited the enzyme. Active components containing in most of the hit samples were hydrophillic. Fumaric acid or small organic compounds or inorganic salts showed the inhibitory activity was suggested. On the other hand, two hydrophobic active compounds were found in the hit samples. One was (4E)-5-(2-methylphenyl)-4-pentenoic acid from a broth of Streptomyces sp. This was the first NADH-fumarate reductase inhibitor produced by actinomycetes. Anothers were pentaene compounds, prugosene A1 and two new analogs isolated from cultured broth of Penicillium sp FKI-5329. They showed strong inhibitory activity against NADH-fumarate reductase.

Research Products

• [Journal Article] Ukulactones A and B, new NADH-fumarate reductase inhibitors produced by Penicillium sp.
  • Author(s): Mori M., Morimoto, H., Kim, Y-P., Ui, H., Nonaka, K., Masuma, R., Sakamoto, K., Kita, K., Tomoda, H., Shiomi, K., Omura, S.
  • Journal Title: FKI-3389. Tetrahedron in press.
  • Peer Reviewed
• [Presentation] 微生物が生産するNADH-フマル酸還元酵素阻害物質の探索 (2011)
  • Author(s): 大山公成、森美穂子、増間碌郎、高橋洋子、大村智、塩見和朗
  • Organizer: 日本農芸化学会2011年度大会(要旨のみ)
  • Place of Presentation: 京都女子大学
  • Year and Date: 2011-03-26
• [Presentation] 微生物が生産するNADH-フマル酸還元酵素阻害活性物質の探索 (2010)
  • Author(s): 大山公成、森美穂子、増間碌郎、高橋洋子、大村智、塩見和朗
  • Organizer: 第4回蠕虫研究会
  • Place of Presentation: 青島サンクマール(宮崎)
  • Year and Date: 2010-11-27
• [Presentation] 微生物が生産するNADH-フマル酸還元酵素阻害物質の探索 (2010)
  • Author(s): 大山公成、森美穂子、増間碌郎、高橋洋子、大村智、塩見和朗
  • Organizer: 第23回バイオサイエンスフォーラム
  • Place of Presentation: 北里大学獣医学部
  • Year and Date: 2010-08-05
• [Remarks] ホームページ等
• [Remarks] 北里生命科学研究所 生物機能研究室HP
  • URL: http://www.kitasato-u.ac.jp/lisci/labo/BioFuncWeb/Index.html
• [Remarks]
  • URL: http://www.kitasato-u.ac.jp/lisci/labo/BioFuncWeb/Index.html