Application of microbial metabolite fraction library and NPPlot on discovery of new metabolites

• Project/Area Number: 26450148
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Nogawa Toshihiko 国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (40462717)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 微生物代謝産物 / フラクションライブラリー / スペクトルデータベース / NPPlot

Outline of Final Research Achievements

The final goal of this project is to construct an efficient method for isolating new secondary metabolites from microbes and to isolate new compounds based on the methodology constructed here. For this purpose, following 4 tasks were carried out: (1) construction of a fraction library, (2) PDA-LC/MS analysis of the library, (3) construction of a spectral database named NPPlot, and (4) isolation of new metabolites from the library. As the results, a fraction library containing over 2,000 fractions was constructed from 30 L culture broths of several microbes. The library was analyzed by PDA-LC/MS for constructing the NPPlot. Several new compounds were isolated from the library by NPPlot screening, and the results were presented in conferences and published in academic journals. Through the project, I confirmed the efficiency of the method for isolating new metabolites from microbes.

Research Products

• [Journal Article] RK-144171, a new benadrostin derivative produced by Streptomyces sp. RK88-1441. (2017)
  • Author(s): Jang JP, Takahashi S, Futamura Y, Nogawa T, Jang JH, Ahn JS, Osada H
  • Journal Title: J Antibiot Volume: 70 Issue: 1 Pages: 102-104
  • DOI: 10.1038/ja.2016.65
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Opantimycin A, a new metabolite isolated from Streptomyces sp. RK88-1355 (2017)
  • Author(s): Nogawa T, Okano A, Lim CL, Futamura Y, Shimizu T, Takahashi S, Ibrahim D, Osada H
  • Journal Title: The Journal of Antibiotics Volume: 70 Pages: 222-225
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Trachyspic acid 19-butyl ester, a new inhibitor of Plk1 polo box domain-dependent recognition from uncharacterized fungus RKGS-F2684. (2017)
  • Author(s): Nogawa T, Ogita N, Futamura Y, Negishi S, Watanabe N, Osada H
  • Journal Title: J Antibiot Volume: 70 Issue: 5 Pages: 705-707
  • DOI: 10.1038/ja.2016.167
  • Peer Reviewed
• [Journal Article] Octaminomycins A and B, Cyclic Octadepsipeptides Active against Plasmodium falciparum. (2017)
  • Author(s): Jang JP, Nogawa T, Futamura Y, Shimizu T, Hashizume D, Takahashi S, Jang JH, Ahn JS, Osada H
  • Journal Title: J Nat Prod Volume: 80 Issue: 1 Pages: 134-140
  • DOI: 10.1021/acs.jnatprod.6b00758
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Stachybotrysin, an Osteoclast Differentiation Inhibitor from the Marine-Derived Fungus Stachybotrys sp. KCB13F013. (2016)
  • Author(s): Kim JW, Ko SK, Kim HM, Kim GH, Son S, Kim GS, Hwang GJ, Jeon ES, Shin KS, Ryoo IJ, Hong YS, Oh H, Lee KH, Soung NK, Hashizume D, Nogawa T, Takahashi S, Kim BY, Osada H, Jang JH, Ahn JS
  • Journal Title: J Nat Prod Volume: 79 Issue: 10 Pages: 2703-2708
  • DOI: 10.1021/acs.jnatprod.6b00641
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Unantimycin A, a new neoantimycin analog isolated from a microbial metabolite fraction library (2016)
  • Author(s): Lim CL., Nogawa T., Okano A., Futamura Y., Kawatani M., Takahashi S. Ibrahim D., Osada H.
  • Journal Title: The Journal of Antibiotics Volume: AOP Issue: 6 Pages: 456-458
  • DOI: 10.1038/ja.2015.124
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of middle chain fatty acyl-CoA ligase responsible for the biosynthesis of 2-alkylmalonyl-CoA for polyketide extender unit (2015)
  • Author(s): Miyazawa T., Takahashi S., Kawata A., Panthee S., Hayashi T., Shimizu T., Nogawa T., Osada H.
  • Journal Title: The Journal of Biological Chemistry Volume: 290 Issue: 45 Pages: 26994-27011
  • DOI: 10.1074/jbc.m115.677195
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] RK-270A-C, new oxindole derivatives isolated from a microbial metabolites fraction library of Streptomyces sp. RK85-270. (2015)
  • Author(s): Jang JP, Nogawa T, Uramoto M, Okano A, Futamura Y, Shimizu T, Takahashi S, Jang JH, Ahn JS, Osada H.
  • Journal Title: J Antibiot (Tokyo) Volume: 68 Issue: 4 Pages: 293-295
  • DOI: 10.1038/ja.2014.141
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of malaria parasite growth by quinomycin A and its derivatives through DNA-intercalating activity. (2015)
  • Author(s): Hayase H, Watanabe N, Lim CL, Nogawa T, Komatsuya K, Kita K, Osada H.
  • Journal Title: Biosci Biotechnol Biochem Volume: 79 Issue: 4 Pages: 633-635
  • DOI: 10.1080/09168451.2014.987205
  • Peer Reviewed / Open Access
• [Journal Article] A new enzyme involved in the control of the stereochemistry in the decalin formation during equisetin biosynthesis. (2015)
  • Author(s): Kato N, Nogawa T, Hirota H, Jang JH, Takahashi S, Ahn JS, Osada H.
  • Journal Title: Biochem Biophys Res Commun Volume: 460 Issue: 2 Pages: 210-215
  • DOI: 10.1016/j.bbrc.2015.03.011
  • NAID: 130007491120
  • Peer Reviewed / Open Access
• [Journal Article] NPPlot（Natural Products Plot）を活用した天然化合物の探索 (2014)
  • Author(s): 野川俊彦、長田裕之
  • Journal Title: 化学と生物 Volume: 52 Pages: 395-402
  • NAID: 130005072117
  • Peer Reviewed / Open Access
• [Journal Article] Structure-function analyses of cytochrome P450revI involved in reveromycin A biosynthesis and evaluation of the biological activity of its substrate, reveromycin T (2014)
  • Author(s): Shunji Takahashi, Shingo Nagano, Toshihiko Nogawa, Naoki Kanoh, Masakazu Uramoto, Makoto Kawatani, Yoshitsugu Shiro, Hiroyuki Osada
  • Journal Title: Journal of Biological Chemistry Volume: 289 Issue: 47 Pages: 32446-32458
  • DOI: 10.1074/jbc.m114.598391
  • Peer Reviewed / Open Access
• [Presentation] Application of microbial and plant metabolites fraction library for a chemical biology study (2017)
  • Author(s): Osada H, Nogawa T
  • Organizer: RIKEN-USM URICAS Symposium 2017
  • Place of Presentation: マレーシア科学大学（マレーシア・ペナン）
  • Year and Date: 2017-02-27
• [Presentation] Application of a fraction library for new metabolites search (2017)
  • Author(s): Nogawa T, Okano A, Otaka J, Osada H
  • Organizer: CSRS-ITbM joint workshop
  • Place of Presentation: 名古屋大学（愛知県・名古屋）
• [Presentation] 放線菌Streptomyces sp. RK88-1355より単離した新規opantimycin Aの構造 (2016)
  • Author(s): 野川俊彦、リム・チュンリャン、岡野亜紀子、二村友史、清水猛、高橋俊二、長田裕之
  • Organizer: 第58回天然有機化合物討論会
  • Place of Presentation: 東北大学（宮城県・仙台）
  • Year and Date: 2016-09-14
• [Presentation] 微生物フラクションライブラリーより単離した新規ネオアンチマイシン類延滞ウナンチマイシンAの構造 (2016)
  • Author(s): 野川俊彦、Lim CL、岡野亜紀子、二村友史、川谷誠、高橋俊二、Ibrahim D、長田裕之
  • Organizer: 日本農芸化学会2016年度年会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-28
• [Presentation] RK144171, a new benadrostin derivative produced by Streptomyces sp. RK88-1441 (2016)
  • Author(s): Jang JP., Nogawa T., Takahashi S., Ahn JS., Osada H.
  • Organizer: 日本農芸化学会2016年度年会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-28
• [Presentation] Isolation of new metabolites from a microbial metabolites fraction library by NPPlot screening (2015)
  • Author(s): NogawaT., Okano A., Jang JP., Shimizu T., Takahashi S., Osada H.
  • Organizer: 環太平洋国際化学会儀
  • Place of Presentation: （アメリカホノルル）
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] フラクションライブラリーとスペクトルデータベースを利用した新規化合物探索 (2015)
  • Author(s): 野川俊彦、Jang JP、Lim CL、岡野亜紀子、本郷やよい、中村健道、高橋俊二、長田裕之
  • Organizer: 第63回質量分析総合討論会
  • Place of Presentation: つくば国際会議場エポルカつくば（茨城県つくば市）
  • Year and Date: 2015-06-18
• [Presentation] Isolation of new cyclic depsipeptides from a microbial metabolites fraction library by NPPlot screening (2015)
  • Author(s): Jang JP., Nogawa T., Hongo Y., Shimizu T., Okano A., Futamura Y., Takahashi S., Jang JH., Ahn JS., Osada H.
  • Organizer: RIKEN-KRIBB Chemical Biology Joint Symposium
  • Place of Presentation: 理化学研究所（埼玉県和光市）
  • Year and Date: 2015-05-22
  • Int'l Joint Research
• [Presentation] A microbial metabolites fraction library with NPPlot for discovery of new metabolites (2015)
  • Author(s): Nogawa T., Okano A., Lim CL., Osada H.
  • Organizer: RIKEN-Max Plank Joint Research Center for Systems Chemical Biology The Fourth Symposium
  • Place of Presentation: 神戸ポートアイランドセンター（兵庫県神戸市）
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] 微生物代謝産物フラクションライブラリーとスペクトルデータベースを用いた新規化合物の探索 (2015)
  • Author(s): 岡野亜紀子、野川俊彦、高橋俊二、長田裕之
  • Organizer: 第一回産総研・理研 触媒化学分野ジョイントワークショップ
  • Place of Presentation: 理化学研究所（埼玉県和光市）
  • Year and Date: 2015-04-27
• [Presentation] アルコール添加による新規リベロマイシン誘導体の創製と生合成機構の考察 (2015)
  • Author(s): 野川俊彦、高橋俊二、高木海、関山恭代、岡野亜紀子、川谷誠、清水猛、長田裕之
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Isolation of new cyclic depsipeptides from a microbial metabolites fraction library by NPPlot screening (2015)
  • Author(s): Jang JP., Nogawa T., Hongo Y., Shimizu T., Okano A., Futamura Y., Takahashi S., Ahn JS., Osada H.
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] マメ科植物クララSophora flavescensのLC/MSを用いたメタボロミクスによる産地比較 (2015)
  • Author(s): 長田麻由佳、野川俊彦、鈴木龍一郎、高橋俊二、白瀧義明、長田裕之
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Construction of a microbial metabolite fraction library with NPPlot for discovery of novel metabolites (2015)
  • Author(s): Nogawa T., Okano A., Lim CL., Takahashi S., Osada H.
  • Organizer: Natural product discovery & development in the post genomic era
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-01-11 – 2015-01-14
• [Presentation] Verticilactam生合成遺伝子クラスターの解析 (2014)
  • Author(s): 寺井淳高、高橋俊二、野川俊彦、橋本絢子、新家一男、池田治生、川崎寿、長田裕之
  • Organizer: 生物生産工学研究センターシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-12-08
• [Presentation] キノマイシン誘導体はDNA挿入活性で抗マラリア効果を示す (2014)
  • Author(s): 渡邊信元、早瀬大貴、Lim CL、野川俊彦、小松谷啓介、北潔、長田裕之
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川（横浜）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 新規機能性成分探索に向けたじゃがいもフラクションライブラリーの作製 (2014)
  • Author(s): 野川俊彦
  • Organizer: 次世代バレイショセミナー
  • Place of Presentation: 北海道
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] 微生物代謝産物フラクションライブラリーより単下新規環状デプシペプチドの構造 (2014)
  • Author(s): 野川俊彦、Jang JP、本郷やよい、清水猛、浦本昌和、岡野亜紀子、二村友史、高橋俊二、Ahn JS、長田裕之
  • Organizer: 第56回天然有機化合物討論会
  • Place of Presentation: 高知
  • Year and Date: 2014-10-15 – 2014-10-17