Studies on microbial secondary metabolism for development of biosynthetic technology tools

• Project/Area Number: 22603011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: ケミカルバイオロジー
• Research Institution: Tokyo University of Science
• Principal Investigator: HAYAKAWA Yoichi 東京理科大学, 薬学部, 教授 (20208606)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 生合成 / チオアミド / メチレン架橋 / thioviridamide / hatomarubigin / Streptomyces / メチルトランスフェラーゼ

Research Abstract

The genome analysis of a thioviridamide-producing organism revealed a gene encoding the thioviridamide precursor peptide (tvaA). Heterologous production of thioviridamide by 15 genes (tvaA- tvaO) identified the thioviridamide biosynthetic gene cluster including thioamide-forming genes. In the hatomarubigin biosynthetic gene cluster, hrbYand hrbUwere identified as a methylene-bridge forming gene and a methyltransferase gene, respectively. The hrbF-deficient gene cluster produced 5-hydroxyhatomarubigin E, suggesting that hrbFcontrols the hydroxylation regioselectivity.

Research Products

• [Journal Article] Production of hatomarubigins by heterologous expression of the hrb gene cluster (2013)
  • Author(s): Masumi Izawa
  • Journal Title: The Journal of Antibiotics Volume: 66
  • Peer Reviewed
• [Journal Article] Biverlactones A-D, new circumventors of arbekacin resistance in MRSA (2011)
  • Author(s): Masato Iwatsuki, Toshiya Ishimori, Tsuyoshi Yamamoto, Keiko Takata, Mihoko Mori, Kenichi Nonaka, Rokuro Masuma, Yoichi Hayakawa, Hideaki Hanaki, Kazuro Shiomi, Satoshi Omura
  • Journal Title: Penicillium sp Volume: 67 Pages: 6644-6648
  • Peer Reviewed
• [Journal Article] Biverlactones A-D, new circumventors of arbekacin resistance in MRSA, produced by Penicillium sp.FKI-4429 (2011)
  • Author(s): M.Iwatsuki, T.Ishimori, T.Yamamoto, K.Takata, M.Mori, K.Nonaka, R.Masuma, Y.Hayakawa, H.Hanaki, K.Shiomi, S.Omura
  • Journal Title: Tetrahedron Volume: 67 Issue: 35 Pages: 6644-6648
  • DOI: 10.1016/j.tet.2011.05.061
  • Peer Reviewed
• [Journal Article] a biosynthetic intermediate of hatomarubigins C and a substrate of HrbU O-methyltransferase (2010)
  • Author(s): Takashi Kawasaki, Yuki Yamada, Tomoka Maruta, Ayumi Maeda, Yoichi Hayakawa: Hatomarubigin E
  • Journal Title: J. Antibiot. Volume: 63 Pages: 725-727
  • Peer Reviewed
• [Journal Article] Flaviogeranin, a new neuroprotective compound from Streptomycessp. (2010)
  • Author(s): Yoichi Hayakawa, Yumi Yamazaki, Maki Kurita, Takashi Kawasaki, Motoki Takagi, Kazuo Shin-ya
  • Journal Title: J. Antibiot. Volume: 63 Pages: 379-380
  • Peer Reviewed
• [Journal Article] Cloning and characterization of a gene cluster for hatomarubigin biosynthesis in Streptomycessp (2010)
  • Author(s): Takashi Kawasaki, Reiko Hirashima, Tomoka Maruta, Haruka Sato, Ayumi Maeda, Yuki Yamada, Maho Takeda, Yoichi Hayakawa
  • Journal Title: strain 2238-SVT4. Appl. Environ. Microbiol. Volume: 76 Pages: 4201-4206
  • Peer Reviewed
• [Journal Article] Cloning and characterization of a gene cluster for hatomarubigin biosynthesis in Streptomyces sp.strain 2238-SVT4 (2010)
  • Author(s): Takashi Kawasaki
  • Journal Title: Applied and Environmental Microbiology Volume: 76 Pages: 4201-4206
  • Peer Reviewed
• [Journal Article] Flaviogeranin, a new neuroprotective compound from Streptomyces sp. (2010)
  • Author(s): Yoichi Hayakawa
  • Journal Title: The Journal of Antibiotics Volume: 63 Pages: 379-380
  • NAID: 10030708860
  • Peer Reviewed
• [Journal Article] Hatomarubigin E, a biosynthetic intermediate of hatomarubigins C and a substrate of HrbU O-methyltransferase (2010)
  • Author(s): Takashi Kawasaki
  • Journal Title: The Journal of Antibiotics Volume: 63 Pages: 725-727
  • Peer Reviewed
• [Presentation] 異種発現系を用いたhatomarubigin類の生産 (2013)
  • Author(s): 伊澤真澄、前田鮎美、木股祥子、川崎崇、早川洋一
  • Organizer: 日本薬学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-29
• [Presentation] 含チオアミド抗生物質thioviridamideの生合成研究 (2013)
  • Author(s): 渡邉安希子、伊澤真澄、川崎崇、早川洋一
  • Organizer: 日本薬学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-29
• [Presentation] 異種発現系を用いたhatomarubigin類の生産 (2013)
  • Author(s): 伊澤真澄
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: 横浜
• [Presentation] 含チオアミド抗生物質thioviridamideの生合成研究 (2013)
  • Author(s): 渡邉安希子
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: 横浜
• [Presentation] Hatomarubigin生合成遺伝子の機能解析 (2012)
  • Author(s): 伊澤真澄、前田鮎美、川崎崇、早川洋一
  • Organizer: 日本農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] Hatomarubigin生合成遺伝子の機能解析 (2012)
  • Author(s): 伊澤真澄
  • Organizer: 日本農芸化学会大会
  • Place of Presentation: 京都女子大学(京都市)
  • Year and Date: 2012-03-23
• [Presentation] Hatomarubiginの生合成に関する研究 (2010)
  • Author(s): 川崎崇、平島麗子、山田佑樹、武田真歩、丸田智加、前田鮎美、佐藤はるか、中井恵美、早川洋一
  • Organizer: 天然有機化合物討論会
  • Place of Presentation: 静岡
  • Year and Date: 2010-09-30
• [Presentation] Hatomarubiginの生合成に関する研究 (2010)
  • Author(s): 川崎崇
  • Organizer: 天然有機化合物討論会
  • Place of Presentation: グランシップ(静岡市)
  • Year and Date: 2010-09-30
• [Presentation] Hatomarubigin生合成遺伝子の機能解析 (2010)
  • Author(s): 川崎崇、平島麗子、山田佑樹、武田真歩、前田鮎美、早川洋一
  • Organizer: 日本放線菌学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-02