Biosynthesis of natural antitumor agents and their rationally engineered analogs in Escherichia coli

• Project/Area Number: 21780106
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: University of Shizuoka
• Principal Investigator: WATANABE Kenji University of Shizuoka, 薬学部, 准教授 (50360938)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 天然物化学 / 化学生物学 / 天然物 / 生合成 / 抗生物質 / 異種発現 / ペプチド / 酵素 / 物質生産 / サフラマイシン / 遺伝子 / 酵母 / 非リボソーム依存性ペプチド

Research Abstract

Biosynthesis of natural antitumor agents and their rationally engineered analogs in Escherichia coli

Research Products

• [Journal Article] 生合成マシナリーを用いた抗腫瘍性物質生産の試み,バイオサイエンスとインダストリー (2011)
  • Author(s): 渡辺賢二, 大栗博毅, 及川英秋
  • Journal Title: バイオインダストリー協会 69 Pages: 26-30
• [Journal Article] 生合成マシナリーを用いた抗腫瘍性物質生産の試み (2011)
  • Author(s): 渡辺賢二
  • Journal Title: バイオサイエンスとインダストリー Volume: 69 Pages: 26-30
  • NAID: 10027617152
• [Journal Article] Intriguing substrate tolerance of epoxide hydrolase Lsd19 involved in biosynthesis of the ionophore antibiotic lasalocid A. (2010)
  • Author(s): Matsuura, Y., Shichijo, Y., Minami, A., Migita, A., Oguri, H., Watanabe, M., Tokiwano, T., Watanabe, K., Oikawa, H.
  • Journal Title: Org.Lett. 12 Pages: 2226-2229
• [Journal Article] Reconstruction of the saframycin core scaffold defines dual Pictet-Spengler mechanisms. (2010)
  • Author(s): Koketsu, K., Oguri, H., Watanabe, K., Oikawa, H.
  • Journal Title: Nature Chemical Biology 6 Pages: 408-410
  • NAID: 120002646838
• [Journal Article] Plasmid construction using recombination activity in the fission yeast Schizosaccharomyces pombe. (2010)
  • Author(s): Chino, A., Watanabe, K., Moriya, M.
  • Journal Title: PLoS One 5
• [Journal Article] Involvement of common intermediate L-3-hydroxyknyurenine in the chromophore biosynthesis of quinomycin family antibiotics. (2010)
  • Author(s): Hirose, Y.
  • Journal Title: J.Antibiot.
  • Peer Reviewed
• [Journal Article] Intriguing substrate tolerance of epoxide hydrolase Lsd19 involved in biosynthesis of the ionophore antibiotic lasalocid A. (2010)
  • Author(s): Matsuura, Y.
  • Journal Title: Org.Lett. Volume: 12 Pages: 2226-2229
  • Peer Reviewed
• [Journal Article] Reconstruction of the saframycin core scaffold defines dual Pictet-Spengler mechanisms. (2010)
  • Author(s): Koketsu, K.
  • Journal Title: Nature Chemical Biology Volume: 6 Pages: 408-410
  • Peer Reviewed
• [Journal Article] A comprehensive overview on genomically directed assembly of aromatic polyketides and macrolide lactones using fungal megasynthases. (2010)
  • Author(s): Saruwatari, T.
  • Journal Title: J.Antibiot.
  • Peer Reviewed
• [Journal Article] Sequence and analysis of the SF2575 gene cluster and characterization of key tailoring enzyme. (2009)
  • Author(s): Pickens, L.B., Wang, P., Zhou, H., Kim, W., Watanabe, K., Gomi, S., Tang, Y.
  • Journal Title: J.Am.Chem.Soc. 131 Pages: 17677-17689
• [Journal Article] Escherichia coli allows efficient modular incorporation of newly isolated quinomycin biosynthetic enzyme into echinomycin biosynthetic pathway for rational design and synthesis of potent antibiotic unnatural natural product. (2009)
  • Author(s): Watanabe, K., Hotta, K., Nakaya, M., Praseuth, A.P., Wang, C.C.C., Inada, D., Takahashi, K., Fukushi, F., Oguri, H., Oikawa, H.
  • Journal Title: J.Am.Chem.Soc. 131 Pages: 9347-9353
• [Journal Article] Rationally Engineered Total Biosynthesis of a Synthetic Analog of a Natural Quinomycin Depsipeptide in Escherichia coli. (2009)
  • Author(s): Watanabe, K., Hotta, K., Praseuth, A.P., Searcey, M., Wang, C.C.C., Oguri, H., Oikawa, H.
  • Journal Title: ChemBioChem 10 Pages: 1965-1968
• [Journal Article] Chromatin-level regulation of biosynthetic gene clusters. (2009)
  • Author(s): Bok, J.W., Chiang, Y. M., Szewczyk, E., Reyes-Domingez, Y., Davidson, A.D., Sanchez, J.F., Lo, H.C., Watanabe, K., Strauss, J., Oakley, B.R., Wang, C.C.C., Keller, N.P.
  • Journal Title: Nature Chemical Biology 5 Pages: 462-464
• [Journal Article] Identification of a gene cluster of polyether antibiotic lasalocid from Streptomyces lasaliensis. (2009)
  • Author(s): Migita, A., Watanabe, M., Hirose, Y., Watanabe, K., Tokiwano, T., Kinashi, H., Oikawa, H.
  • Journal Title: Biosci.Biotechnol.Biochem. 73 Pages: 169-176
  • NAID: 10027536367
• [Journal Article] Enzymatic synthesis of molecular skeletons of complex antitumor antibiotics with non-ribosomal peptide synthetases. (2009)
  • Author(s): Watanabe, K., Oguri, H, Oikawa, H.
  • Journal Title: Journal of Synthetic Organic Chemistry,Japan 67 Pages: 1152-1160
  • NAID: 10026866717
• [Journal Article] Genetic indoctrination of Escherichia coli for innovative drug discovery by way of heterologous expression of the echinomycin biosynthetic pathway. (2009)
  • Author(s): Watanabe, K., Oguri, H., Oikawa, H.
  • Journal Title: Current Opinion in Chemical Biology 13 Pages: 189-196
• [Journal Article] Escherichia coli allows efficient modular incorporation of newly isolated quinomycin biosynthetic enzyme into echinomycin biosynthetic pathway for rational design and synthesis of potent antibiotic unnatural product (2009)
  • Author(s): Watanabe, K., et al.
  • Journal Title: J Am Chem Soc 131 Pages: 9347-9353
  • Peer Reviewed
• [Journal Article] Rationally engineered total biosynthesis of a synthetic analogue of natural quinomycin depsipeptide in Escherichia coli (2009)
  • Author(s): Watanabe, K., et al.
  • Journal Title: ChembioChem 10 Pages: 1965-1968
  • Peer Reviewed
• [Journal Article] Involvement of common intermediate L-3-hydroxyknyurenine in the chromophore biosynthesis of quinomycin family antibiotics.
  • Author(s): Hirose, Y., Watanabe, K., Minami, A., Nakamura, T., Oguri, H., Oikawa, H.
  • Journal Title: J.Antibiot. in press.
• [Journal Article] A comprehensive overview on genomically directed assembly of aromatic polyketides and macrolide lactones using fungal megasynthases.
  • Author(s): Saruwatari, T., Praseuth, A. P., Sato, M., Torikai, K., Noguchi, H., Watanabe, K.
  • Journal Title: J.Antibiot. in press.
  • NAID: 10030637198
• [Presentation] 生合成遺伝子の発現による抗腫瘍活性物質サフラマイシンの効率的合成 (2011)
  • Author(s): 猿渡隆佳
  • Organizer: 日本薬学会
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] スプライソソーム非依存型ゲノムDNAの発現によるポリケタイド系天然物の新規探索法 (2011)
  • Author(s): 石川格靖
  • Organizer: 日本薬学会
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] 酵母を宿主としたポリケタイド合成システムの構築 (2011)
  • Author(s): 大熊貴士
  • Organizer: 日本薬学会
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] 生合成遺伝子の発現による抗腫瘍活性物質サフラマイシンの効率的合成 (2011)
  • Author(s): 猿渡隆佳
  • Organizer: 日本薬化学会
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] スプライソソーム非依存型ゲノムDNAの発現によるポリケタイド系天然物の新規探索法 (2011)
  • Author(s): 石川格靖
  • Organizer: 日本薬化学会
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] 酵母を宿主としたポリケタイド合成システムの構築 (2011)
  • Author(s): 大熊貴士
  • Organizer: 日本薬化学会
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] 生合成遺伝子の発現による抗腫瘍活性物質サフラマイシンの効率的合成 (2011)
  • Author(s): 猿渡隆佳
  • Organizer: 日本農芸化学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-03-27
• [Presentation] スプライソソーム非依存型ゲノムDNAの発現によるポリケタイド系天然物の新規探索法 (2011)
  • Author(s): 石川格靖
  • Organizer: 日本農芸化学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-03-27
• [Presentation] 酵母を宿主としたポリケタイド合成システムの構築 (2011)
  • Author(s): 小林竜太
  • Organizer: 日本農芸化学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-03-27
• [Presentation] スプライソソーム非依存型ゲノムDNAの発現によるポリケチド系天然物の新規探索法 (2010)
  • Author(s): 猿渡隆佳
  • Organizer: 日本薬学会東海支部会
  • Place of Presentation: 静岡市
  • Year and Date: 2010-11-28
• [Presentation] 生合成遺伝子の大腸菌発現による抗腫瘍性生理活性物質サフラマシンの効率的合成 (2010)
  • Author(s): 渡辺賢二
  • Organizer: アステラス病態研究会
  • Place of Presentation: 経団連会館,東京
  • Year and Date: 2010-10-16
• [Presentation] 天然物合成を指向した生合成遺伝子の異種発現によるシンセティックバイオロジーの確立 (2010)
  • Author(s): 渡辺賢二
  • Organizer: バイオインダストリー協会
  • Place of Presentation: パシフィコ横浜,横浜
  • Year and Date: 2010-09-29
• [Presentation] 合理的設計に基づく改変生合成遺伝子群を用いた非天然型生物活性環状デプシペプチドの合成 (2010)
  • Author(s): 渡辺賢二
  • Organizer: 生体触媒化学シンポジウム
  • Place of Presentation: 静岡市
  • Year and Date: 2010-09-24
• [Presentation] スプライソソーム非依存型ゲノムDNAの発現によるポリケチド系天然物の新規探索法 (2010)
  • Author(s): 猿渡隆佳
  • Organizer: 生体触媒化学シンポジウム
  • Place of Presentation: 静岡市
  • Year and Date: 2010-09-24
• [Presentation] Rational Design of Natural Products through Controlled Biosynthesis (2009)
  • Author(s): Kenji Watanabe
  • Organizer: 5th Japan-Korea Young Scientists Meeting on Bioorganic and Natural Products Chemistry
  • Place of Presentation: Shizuoka, JAPAN
• [Presentation] Rational Design of Natural Products through Controlled BiosynthesisSociety for Industrial Microbiology (2009)
  • Author(s): Kenji Watanabe
  • Organizer: Annual meeting and exhibition 2009
  • Place of Presentation: Westin Harbour Castle Hotel, Toronto, ON, Canada
• [Book] 天然物全合成の最新動向(生合成酵素による天然物の全合成-抗腫瘍性物質エキノマイシンの合成を中心に-)(北泰行監修) (2009)
  • Author(s): 渡辺賢二, 大栗博毅, 及川英秋
  • Publisher: シーエムシー出版
• [Book] Complex enzymes : overview and peptides(Assembling nonribosomal peptide gene cluster in a heterologous host.)(edited by David Hopwood.) (2009)
  • Author(s): Watanabe, K., Praseuth, A.P., Praseuth, M.B., Hotta, K.
  • Publisher: Methods in Enzymology
• [Remarks] ホームページ等
  • URL: http://www015.upp.so-net.ne.jp/kenji55-lab/
• [Remarks]
  • URL: http://www015.upp.so-net.ne.jp/kenji55-lab/
• [Patent(Industrial Property Rights)] カビ類ポリケチド合成遺伝子の酵母での異種発現 (2010)
  • Inventor(s): 渡辺賢二、守屋央朗
  • Industrial Property Rights Holder: 静岡県立大学、岡山大学
  • Filing Date: 2010-08-13
• [Patent(Industrial Property Rights)] カビ類ポリケチド合成遺伝子の酵母での異種発現 (2010)
  • Inventor(s): 渡辺賢二, 守屋央朗
  • Industrial Property Rights Holder: 静岡県立大学, 岡山大学
  • Industrial Property Number: 2010-181279
  • Filing Date: 2010-08-13