Genome mining and microbial production of secondary metabolites

• Project/Area Number: 21688009
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: University of Shizuoka (2010-2011); The University of Tokyo (2009)
• Principal Investigator: FUNA Nobutaka 静岡県立大学, 食品栄養科学部, 准教授 (70361574)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
• Keywords: ポリケタイド / III型ポリケタイド合成酵素 / クルクミン / Streptomyces / Oryza sativa / アルキルレゾルシノール / ウコン / 放線菌

Research Abstract

Genome mining is an innovative approach to isolating novel natural products by utilizing the genome data of bacteria, fungi, and plants. We characterized novel type I and type III polyketide synthases by genome mining studies of Streptomyces, Aspergillus, and Oryza sativa. We manipulated polyketide biosynthesis to generate libraries of "unnatural" natural products by microorganisms.

Research Products

• [Journal Article] The omethyltransferase SrsB catalyzes the decarboxylative methylation of alkylresorcylic acid during phenolic lipid biosynthesis by Streptomyces griseus (2012)
  • Author(s): Nakano, C., Funa, N., Ohnishi, Y., and Horinouchi, S
  • Journal Title: J. Bacteriol Volume: 194 Issue: 6 Pages: 1544-1551
  • DOI: 10.1128/jb.06406-11
  • Peer Reviewed
• [Journal Article] Fatty acyl-AMP ligase involvement in the production of alkylresorcylic acid by a Myxococcus xanthus type III polyketide synthase (2011)
  • Author(s): Hayashi, T., Kitamura, Y., Funa, N., Ohnishi, Y. and Horinouchi, S
  • Journal Title: Chembiochem Volume: 12 Issue: 14 Pages: 2166-2176
  • DOI: 10.1002/cbic.201100344
  • Peer Reviewed
• [Journal Article] Alkylresorcylic acidsynthesis bytype III polyketide synthase from Oryza sativa (2010)
  • Author(s): Matsuzawa, M., Katsuyama, Y., Funa, N., and Horinouchi, S
  • Journal Title: Phytochemistry Volume: 71 Issue: 10 Pages: 1059-1067
  • DOI: 10.1016/j.phytochem.2010.02.012
  • Peer Reviewed
• [Journal Article] Precursor-Directed Biosynthesis of Curcumin Analogs in Escherichia coli (2010)
  • Author(s): Katsuyama, Y., Hirose, Y., Funa, N., Ohnishi, Y., and Horinouchi, S
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 74 Issue: 3 Pages: 641-645
  • DOI: 10.1271/bbb.90866
  • NAID: 10027553119
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] Alkylresorcylic acid synthesis by type III polyketide synthases from rice Oryza sativa. (2010)
  • Author(s): Miku Matsuzawa
  • Journal Title: Phytochemistry Volume: 71 Pages: 1059-1067
  • Peer Reviewed
• [Journal Article] Precursor-directed biosynthesis of curcumin analogs in Escherichia coli (2010)
  • Author(s): Youhei Katsuyama
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 74 Pages: 641-645
  • Peer Reviewed
• [Journal Article] Physically discreteβ-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase (2009)
  • Author(s): Awakawa, T., Yokota, K., Funa, N., Doi, F., Mort, N., Watanabe, H., and Horinouchi, S
  • Journal Title: Chem. Biol Volume: 16 Issue: 6 Pages: 613-623
  • DOI: 10.1016/j.chembiol.2009.04.004
  • Peer Reviewed
• [Journal Article] Biosynthesis of Aliphatic Polyketides by Type III Polyketide Synthase and Methyltransferase in Bacillus subtilis (2009)
  • Author(s): Nakano, C., Ozawa, H., Akanuma, G., Funa, N., and Horinouchi, S
  • Journal Title: J. Bacteriol Volume: 191 Issue: 15 Pages: 4916-4923
  • DOI: 10.1128/jb.00407-09
  • Peer Reviewed
• [Journal Article] Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa (2009)
  • Author(s): Katsuyama, Y., Kita, T., Funa, N., and Horinouchi, S
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 11160-11170
  • Peer Reviewed
• [Journal Article] Physically discrete β-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase (2009)
  • Author(s): Takayoshi Awakawa
  • Journal Title: Chemistry & Biology 16 Pages: 613-623
  • Peer Reviewed
• [Journal Article] Biosynthesis of aliphatic polyketides by type III polyketide synthase and methyltransferase in Bacillus subtilis (2009)
  • Author(s): Chiaki Nakano
  • Journal Title: Journal of Bacteriology 191 Pages: 4916-4923
  • Peer Reviewed
• [Journal Article] Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa (2009)
  • Author(s): Youhei Katsuyama
  • Journal Title: Journal of Biological Chemistry 284 Pages: 11160-11170
  • Peer Reviewed
• [Presentation] Rhodococcus jostii RHA1株におけるβ-ケトアジピン酸経路の新規バイパス経路の解析 (2012)
  • Author(s): 山梨智也
  • Organizer: 日本農芸化学会大会2012
  • Place of Presentation: 京都女子大学(京都府)
  • Year and Date: 2012-03-24
• [Presentation] Microbial production of plant polyketides by utilizing diversereactions of type III polyketide synthases (2011)
  • Author(s): Nobutaka Funa
  • Organizer: IUMS(International Congress of Bacteriology and Applied Microbiology)
  • Place of Presentation: Hokkaido, Japan
  • Year and Date: 2011-09-09
• [Presentation] Microbial production of plant polyketides by utilizing diverse reactions of type III polyketide synthases (2011)
  • Author(s): Nobutaka Funa
  • Organizer: International Congress of Bacteriology and Applied Microbiology
  • Place of Presentation: 札幌コンベンションセンター(北海道)(招待講演)
  • Year and Date: 2011-09-09
• [Presentation] Rhodococcus jostii RHAl株におけるβ-ケトアジピン酸経路の新規バイパス経路の解析 (2011)
  • Author(s): 山梨智也、原啓文、鮒信学
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都
• [Presentation] Curcuminoid synthesis by type III polyketide synthases and their application to microbial production of plant polyketides (2010)
  • Author(s): Nobutaka Funa
  • Organizer: Pacifichem 2010
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2010-12-15
• [Presentation] Curcuminoid synthesis by type III polyketide synthases and their application to microbial production of plant polyketides (2010)
  • Author(s): Nobutaka Funa
  • Organizer: Pacifichem 2010
  • Place of Presentation: ハワイ州、アメリカ
  • Year and Date: 2010-12-15
• [Presentation] Aβ-lactamase-type thioesterase responsible for product release in polyketide biosynthesis (2010)
  • Author(s): Nobutaka Funa
  • Organizer: 2010 RIKEN Chemical Biology International Symposium
  • Place of Presentation: Saitama, Japan
  • Year and Date: 2010-10-26
• [Presentation] A β-lactamase-type thioesterase responsible for product release in polyketide biosynthesis (2010)
  • Author(s): Nobutaka Funa
  • Organizer: 2010 RIKEN Chemical Biology International Symposium
  • Place of Presentation: 埼玉
  • Year and Date: 2010-10-26
• [Presentation] ウコン由来クルクミン合成酵素(CURS)の結晶構造解析 (2010)
  • Author(s): 勝山陽平
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-29
• [Presentation] 窒素固定細菌由来III型ポリケタイド合成酵素の環化機構の解析 (2010)
  • Author(s): 佐藤龍太朗
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-29
• [Presentation] Actinoplanes missouriensis 由来の新規テルペノイド-ポリケタイド融合化合物合成に関わる遺伝子クラスターの機能解析 (2010)
  • Author(s): 淡川孝義
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-29
• [Presentation] Myxococcus xanthus 由来の fatty acyl-AMP ligase 依存的 priming 機構を持ったIII型ポリケタイド合成酵素の機能解析 (2010)
  • Author(s): 林貴之
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-29
• [Presentation] I型ポリケタイド合成酵素から生成物を解離するβ-lactamase 型チオエステラーゼの機能解析 (2010)
  • Author(s): 横田康介
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-29
• [Presentation] 組換え大腸菌と組換え酵母の共培養による非天然型イソフラボンの生産 (2010)
  • Author(s): 松井美里
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] 「組換え大腸菌と組換え酵母の共培養による非天然型イソフラボンの生産」 (2010)
  • Author(s): 勝山陽平、松井美里、鮒信学、大西康夫、堀之内末治
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] 1型ポリケタイド合成酵素から生成物を解離するβ-1actamse型チオエステラーゼの機能解析 (2010)
  • Author(s): 淡川孝義、横田康介、鮒信学、大西康夫、堀之内末治
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] Myxococcus xanthus由来のfattyacyl-AMP ligase依存的priming機構を持ったIII型ポリケタイド合成酵素の機能解析 (2010)
  • Author(s): 林貴之、鮒信学、大西康夫、堀之内末治
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] Actinoplanes missouriensis由来の新規テルペノイドーポリケタイド融合化合物合成に関わる遺伝子クラスターの機能解析 (2010)
  • Author(s): 淡川孝義、鮒信学、藤田信之、早川正幸、大西康夫、堀之内末治
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] 窒素固定細菌由来III型ポリケタイド合成酵素の環化機構の解析 (2010)
  • Author(s): 佐藤龍太朗、宮永顕正、小沢弘樹、鮒信学、宮園健一、田之倉優、大西康夫、堀之内末治
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] ウコン由来クルクミン合成酵素(CURS)の結晶構造解析 (2010)
  • Author(s): 勝山陽平、宮園健一、鮒信学、田之倉優、大西康夫、堀之内末治
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] Combinatorial biosynthesis of plant medicinal polyketides in microorganisms (2009)
  • Author(s): Nobutaka Funa
  • Organizer: 25^<th> Naito Conference
  • Place of Presentation: Hokkaido, Jappan
  • Year and Date: 2009-09-11