Screening of natural products which inhibits a new menaquinone biosynthetic pathway

2012 Fiscal Year Final Research Report

• Project/Area Number: 22310139
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Hokkaido University
• Principal Investigator: DAIRI Tohru 北海道大学, 大学院・工学研究院, 教授 (70264679)
• Project Period (FY): 2010 – 2012
• Keywords: 微生物 / メナキノン / 生合成 / フタロシン経路 / 阻害剤

Research Abstract

The futalosine pathway is operating in some bacteria for the biosynthesis of menaquinone. Futalosine is converted into dehypoxanthinyl futalosine (DHFL) by MqnB.In this study, three routes to the formation of DHFL were suggested. DHFL may have been directly formed by MqnB in Thermus thermophilus. In Streptomyces coelicolor, aminodeoxy FL (AFL) was converted to FL by deaminases, then to DHFL. In contrast, MqnB of Helicobacter pylori directly converted AFL into DHFL.
To identify compounds that specifically inhibit the futalosin pathway, we used B. halodurans that has FL pathway as a test strain. Finally, two candidate fungal culture broths were obtained.

Research Products

• [Journal Article] CcpAx is a new member of the cellulose synthase complex (terminal complex) in Acetobacter xylinum (2013)
  • Author(s): N. Sunagawa, T. Fujiwara, T. Yoda, D.Shimura, M. Sakai, S. Kawano, Y. Satoh, M. Yao, K. Tajima, and T. Dairi
  • Journal Title: J. Biosci. Bioeng Volume: (in press)
  • Peer Reviewed
• [Journal Article] Synthesis of (±)-cyclic de-hypoxanthine futalosine, the biosynthetic intermediate in an alternative biosynthetic pathway for menaquinones. (2011)
  • Author(s): A. Yajima, S. Kouno, M. Mogi, R. Katsuta, T. Dairi, H. Seto, and T. Nukada
  • Journal Title: Tetrahedron Lett. Volume: 52 Pages: 4934-4937
  • Peer Reviewed
• [Journal Article] Isolation of a Thermotolerant Bacterium Producing Medium-chain-length Polyhydroxyalkanoate (2011)
  • Author(s): Y. Satoh, K. Tajima, S. Nakamoto, H.Xuerong, T. Matsushima, T. Ohshima, S. Kawano, T. Erata, T. Dairi, and M. Munekata
  • Journal Title: J. Appl. Microbiol. Volume: 111 Pages: 811-817
  • Peer Reviewed
• [Journal Article] Enzymatic polymerization of 2-hydroxyalkanoates: copolymerization of 2-hydroxybutyrate by wild-type class I PHA synthase. (2011)
  • Author(s): X. Han, Y. Satoh, T. Satoh, T. Kakuchi, K.Matsumoto, S. Taguchi, T. Dairi, M. Munekata, and K. Tajima
  • Journal Title: Appl. Microbiol. Biotech. Volume: 92 Pages: 509-517
  • Peer Reviewed
• [Journal Article] Reveromycin A biosynthesis uses RevG and RevJ for stereospecific spiroacetal formation (2011)
  • Author(s): S. Takahashi, A. Toyoda, Y. Sekiyama, H.Takagi, T. Nogawa, M. Uramoto, R. Suzuki, H. Koshino, T. Kumano, S. Panthee, T. Dairi, J. Ishikawa, H. Ikeda, Y. Sakaki, and H. Osada
  • Journal Title: Nat. Chem. Biol. Volume: 7 Pages: 461-468
  • Peer Reviewed
• [Journal Article] Convergent strategies in biosynthesis. (2011)
  • Author(s): T. Dairi, T. Kuzuyama, M. Nishiyama, and Fujii I.
  • Journal Title: Nat. Prod. Rep. Volume: 28 (6) Pages: 1054-1086
  • Peer Reviewed
• [Journal Article] Diversity of the early step of the futalosine pathway. (2011)
  • Author(s): C. Arakawa, K. Furihata, T. Hiratsuka, N.Itoh, H. Seto, and T. Dairi
  • Journal Title: Antimicrob Agents Chemother. Volume: 55 Pages: 913-916
  • Peer Reviewed
• [Journal Article] Dairi, Branched fatty acids inhibit the biosynthesis of menaquinone in Helicobacter pylori. (2011)
  • Author(s): R. Tanaka, T. Kunisada, N. Kushida, K.Yamada, S. Ikeda, M. Noike, Y. Ono, N. Itoh, H. Takami, H. Seto, and T.
  • Journal Title: J. Antibiot. Volume: 64 Pages: 151-153
  • Peer Reviewed
• [Journal Article] 微生物におけるビタミンK生合成の分子機構と生物学的意義 (2011)
  • Author(s): 大利徹
  • Journal Title: 腎と代謝 Volume: 24巻 Pages: 179-186
• [Presentation] 新規メナキノン生合成経路酵素MqnDの生成物・類似体複合体のX線結晶構造解析 (2013)
  • Author(s): 松尾京子、石北央、大利徹、瀬戸治男、新井亮一
  • Organizer: 平成25年度日本農芸化学会大会
  • Place of Presentation: 東北大学
  • Year and Date: 20130300
• [Presentation] An alternative menaquinone biosynthetic pathway: an attractive target for drug discovery to Helicobacter pylori (2012)
  • Author(s): Tohru Dairi
  • Organizer: 17th Malaysian Chemical Congress (17MCC)
  • Place of Presentation: Putra World Trade Centre, Kuala Lumpur, Malaysia.
  • Year and Date: 20121015-17
• [Presentation] 放線菌が持つメナキノン新規生合成経路の解明と特異的阻害剤の探索 (2012)
  • Author(s): 池田駿介、池田安由美、佐藤康治、野池基義、瀬戸治男、大利徹
  • Organizer: 2012年度(第27回)日本放線菌学会大会
  • Place of Presentation: 府中の森芸術劇場
  • Year and Date: 2012-09-06
• [Presentation] 補酵素類の生合成に関与する新規酵素の解析と応用 (2012)
  • Author(s): 大利徹
  • Organizer: 第13回酵素応用シンポジウム
  • Place of Presentation: 名古屋メルパルク
  • Year and Date: 2012-06-08
• [Presentation] 微生物に見出されたメナキノ ン新規生合成経路の全容解明と抗ピロ リ菌薬開発への応用 (2012)
  • Author(s): 大利徹
  • Organizer: 公益財団法人発酵研究所第6回研究報告会
  • Place of Presentation: 千里ライフ サイエンスセンター 大阪
  • Year and Date: 2012-06-07
• [Presentation] 微生物に見出されたメナキノン新規生合成経路の全容解明と抗ピロ リ菌剤の開発 (2012)
  • Author(s): 大利徹
  • Organizer: 公益財団法人野田産業科学研究所、平成24年度研究成果発表会
  • Place of Presentation: 東京会館
  • Year and Date: 2012-06-01
• [Presentation] Microorganisms evolved vitamin biosynthetic enzymes in response to various environments, an example in menaquinone biosynthesis (2011)
  • Author(s): Tohru Dairi
  • Organizer: The IUMS2011, Sapporo
  • Place of Presentation: 札幌国際会議場
  • Year and Date: 20110906-10
• [Presentation] An alternative menaquinone biosynthetic pathway: an attractive target for drug discovery to Helicobacter pylori (2011)
  • Author(s): Tohru Dairi
  • Organizer: The Third International Conference on Cofactors 03 (ICC-03)
  • Place of Presentation: The University of Turku, Finland
  • Year and Date: 20110710-15
• [Presentation] メナキノン(MK)新規生合成経路阻害剤の探索 (2011)
  • Author(s): 田中友理、國定孝夫、櫛田伸明、山田恵子、池田駿介、伊藤伸哉、瀬戸治男、大利徹
  • Organizer: 平成23年度日本農芸化学会大会
  • Place of Presentation: 京都女子大学
  • Year and Date: 20110300
• [Presentation] フタロシン(FL)経路の初発反応の多様性 (2011)
  • Author(s): 荒川知里、倉都将宏、伊藤伸哉、瀬戸治男、大利徹
  • Organizer: 平成23年度日本農芸化学会大会
  • Place of Presentation: 京都女子大学
  • Year and Date: 20110300
• [Presentation] 微生物におけるビタミン生合成経路の多様性 (2011)
  • Author(s): 大利徹
  • Organizer: 生物資源学特別セミナー
  • Place of Presentation: 福井県立大学
  • Year and Date: 2011-05-23
• [Presentation] Studies on the early biosynthetic step of the futalosine (menaquinone) pathway (2010)
  • Author(s): Tohru Dairi
  • Organizer: Pacifichem 2010,Honolulu
  • Place of Presentation: シェラトンワイキキ
  • Year and Date: 2010-12-16
• [Presentation] ピロリ菌が持つ特異的ビタミン生合成経路の解明と抗ピロリ菌薬開発への挑戦 (2010)
  • Author(s): 大利徹
  • Organizer: 第3回北大工学系-道総研連携フォーラム
  • Place of Presentation: 北大創成科学研究棟
  • Year and Date: 2010-10-26
• [Presentation] An alternative menaquinone biosynthetic pathway: an attractive target for drug discovery to pathogenic Helicobacter and Chlamydia strains. (2010)
  • Author(s): Tohru Dairi
  • Organizer: 12th Japanese-Swiss Meeting on Biotechnology and BioprocessDevelopment, Toyama
  • Place of Presentation: 富山国際会議場
  • Year and Date: 2010-10-11
• [Presentation] 放線菌におけるフタロシン経路の初発反応の多様性 (2010)
  • Author(s): 荒川知里、倉都将宏、瀬戸治男、大利徹
  • Organizer: 平成22年度日本放線菌学会大会
  • Place of Presentation: 東京、タワーホール船堀
  • Year and Date: 2010-09-03
• [Presentation] 放線菌が持つメナキノン新規 生合成経路の解明 (2010)
  • Author(s): 大利徹
  • Organizer: 平成22年度日本放線菌学会大会
  • Place of Presentation: 東京、タワーホール船堀
  • Year and Date: 2010-09-02
• [Presentation] 微生物に見出されたメナキノン新規生合成の解明にいたるストーリ ィー (2010)
  • Author(s): 大利徹
  • Organizer: 第45回天然物化学談話会
  • Place of Presentation: 愛知県蒲郡市、ホテル明山荘
  • Year and Date: 2010-07-07
• [Book] Methods in Enzymol (2012)
  • Author(s): T. Dairi
  • Total Pages: 107-122
  • Publisher: Menaquinone biosyntheses in microorganisms
• [Remarks]
  • URL: http://www.eng.hokudai.ac.jp/labo/tre/