Biosynthetic study of manumycin antibiotics for creating novel analogs

• Project/Area Number: 24710253
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Living organism molecular science
• Research Institution: Tokushima Bunri University
• Principal Investigator: ITO Takuya 徳島文理大学, 薬学部, 講師 (90517484)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 放線菌 / mutasynthesis / 生合成 / 遺伝子工学

Research Abstract

Sequence analysis of genome from asukamycin producing strain revealed a gene cluster involve in the biosynthesis of asukamycin. Genetic disruption of cyclohexane synthase (asuB3) and 5-aminolevulinate synthase (asuD2), individually abrogated asukamycin production, this confirmed the involvement of the asu gene cluster in asukamycin biosynthesis. Mutasynthesis approach using these mutants was developed for the generation of novel asukamycin analogs.

Research Products

• [Journal Article] Two novel aromatic glucosides, marylaurencinosides D and E, from the fresh flowers of Cymbidium Great Flower 'Marylaurencin (2014)
  • Author(s): Yoshikawa, K., Okahuji, M., Iseki, K., Ito, T., Asakawa, Y., Kawano, S., Hashimoto, T.
  • Journal Title: J. Nat. Med. Volume: 68 Issue: 2 Pages: 455-458
  • DOI: 10.1007/s11418-013-0814-8
  • Peer Reviewed / Open Access
• [Journal Article] Pungent and bitter, cytotoxic and antiviral terpenoids from some bryophytes and inedible fungi. (2014)
  • Author(s): Asakawa, Y., Nagashima, F., Hashimoto, T., Toyota, M., Ludwiczuk, A., Komala, I., Ito, T., Yagi, Y.
  • Journal Title: Nat. Prod. Commun. Volume: 9 Pages: 409-417
  • Peer Reviewed
• [Journal Article] Biosynthetic Study of Actinomycetes-Metabolites for Creating Novel Analogs (2013)
  • Author(s): Ito, T.
  • Journal Title: YAKUGAKU ZASSHI Volume: 133 Issue: 9 Pages: 1007-1015
  • DOI: 10.1248/yakushi.13-00175
  • NAID: 130003361989
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2013-09-01
  • Peer Reviewed
• [Journal Article] Biosynthetic study of actinomycetes- metabolites for creating novel analogs (2013)
  • Author(s): Ito, T.
  • Journal Title: Yakugaku Zasshi Volume: 133 Pages: 1007-1015
  • NAID: 130003361989
• [Journal Article] Aromatic Constituents of Cymbidium Great Flower Marie Laurencin and their Antioxidative Activity (2013)
  • Author(s): Yoshikawa, K., Otsu, M., Ito, T., Asakawa, Y., Kawano, S., Hashimoto, T.
  • Journal Title: J. Nat. Med Volume: 67 Pages: 217-221
  • NAID: 10031131622
• [Journal Article] Aromatic Constituents of Cymbidium Great Flower Marie Laurencin and their Antioxidative Activity (2013)
  • Author(s): Yoshikawa, K., Otsu, M., Ito, T., Asakawa, Y., Kawano, S., Hashimoto, T.
  • Journal Title: J. Nat. Med. Volume: 67 Issue: 1 Pages: 217-221
  • DOI: 10.1007/s11418-012-0653-z
  • NAID: 10031131622
  • Peer Reviewed
• [Journal Article] Transcriptional Regulation and Increased Production of Asukamycin in Engineered Streptomyces nodosus subsp. asukaensis Strains (2012)
  • Author(s): Xie, P., Sheng, Y., Ito, T., Mahmud, T.
  • Journal Title: Appl. Microbiol. Biotech Volume: 96 Pages: 451-460
• [Journal Article] -hydroxyl fatty acids from a metagenomic library of a marine sponge (2012)
  • Author(s): He, R., Wakimoto, T., Egami, Y., Kenmoku, H., Ito, T., Asakawa, Y., Abe, I.
  • Journal Title: Bioorgan Med. Chem Lett Volume: 22 Pages: 7322-7325
• [Journal Article] Biosynthetic pathway for highly structural diversity of a common dilactone core in antimycin production (2012)
  • Author(s): Yan, Y., Zhang, L., Ito, T., Qu, X., Asakawa, Y., Awakawa, T., Abe, I., Liu, Wen.
  • Journal Title: Org. Lett Volume: 14 Pages: 4142-4145
• [Journal Article] Porphyrins from a metagenomic library of the marine sponge (2012)
  • Author(s): He, R., Wakimoto, T., Takeshige, Y., Egami, Y., Kenmoku, H., Ito, T., Wang, B., Asakawa, Y., Abe, I.
  • Journal Title: Molecular BioSystems Volume: 8 Pages: 2334-2338
• [Journal Article] Phenanthrene Derivatives from Cymbidium Great Flower Marie Laurencin and Their Biological Activities (2012)
  • Author(s): Yoshikawa, K., Ito, T., Iseki, K., Baba,C., Imagawa, H., Yagi, Y., Morita, H., Asakawa,Y., Kawano, S., Hashimoto, T.
  • Journal Title: J. Nat. Prod Volume: 75 Pages: 605-609
• [Journal Article] Heterologously expressed β-hydroxyl fatty acids from a metagenomic library of a marine sponge (2012)
  • Author(s): R. He, T. Wakimoto, Y. Egami, H. Kenmoku, T. Ito, Y. Asakawa, I. Abe
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 22 Issue: 24 Pages: 7322-7325
  • DOI: 10.1016/j.bmcl.2012.10.082
  • Peer Reviewed
• [Journal Article] Biosynthetic pathway for highly structural diversity of a common dilactone core in antimycin production (2012)
  • Author(s): Yan, Y.
  • Journal Title: Organic Letters Volume: 14 Issue: 16 Pages: 4142-4145
  • DOI: 10.1021/ol301785x
  • Peer Reviewed
• [Journal Article] Porphyrins from a metagenomic library of the marine sponge Discodermia calyx (2012)
  • Author(s): He, R.
  • Journal Title: Mol. BioSyst. Volume: 6 Issue: 9 Pages: 2334-2338
  • DOI: 10.1039/c2mb25169h
  • Peer Reviewed
• [Presentation] メディオマイシン生合成遺伝子の同定 (2014)
  • Author(s): 張驪駻, 伊藤卓也, 脇本敏幸, 淡川孝義, 浅川義範, 阿部郁朗
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] 本邦産,マレーシア産およびアルゼンチン産苔類のテルペノイド (2014)
  • Author(s): 長島史裕, 井上進之介, 上田淳也, 新田佳代, 仲松早希, 八木康行, 伊藤卓也, 浅川義範
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] Oridamycin生合成遺伝子のクローニング (2014)
  • Author(s): 川崎崇, 渡邊あゆみ, 伊藤卓也, 今村信孝
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] 本邦産，マレーシア産およびアルゼンチン産苔類のテルペノイド (2014)
  • Author(s): 長島史裕、井上進之介、上田淳也、新田佳代、仲松早希、八木康行、伊藤卓也、浅川義範
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] 放線菌由来新規化合物の探索 (2014)
  • Author(s): 山田陽香、佐藤道大、伊藤卓也、高橋公咲、野口博司、渡辺賢二
  • Organizer: 第60 回日本生薬学会
  • Place of Presentation: 北海道
• [Presentation] (2013)
  • Author(s): 浅川義範, 中山維摩, 伊藤卓也
  • Organizer: 第57回香料・テルペンおよび精油化学に関する討論会
  • Place of Presentation: 埼玉
• [Presentation] 放線菌由来新規化合物の探索 (2013)
  • Author(s): 山田陽香, 佐藤道大, 伊藤卓也, 高橋公咲, 野口博司, 渡辺賢二
  • Organizer: 第60回日本生薬学会
  • Place of Presentation: 北海道
• [Presentation] α-グルコシダーゼ阻害物質トレスタチンの生合成遺伝子群のクローニング (2013)
  • Author(s): 阿部高大, Taifo Mahmud, 兼目祐充, 浅川義範, 伊藤卓也
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] アンチマイシン生合成経路の探索と新規アナログの生産 (2013)
  • Author(s): 張魔騨, Yan YAN, 伊藤卓也, Xudong QU, 淡川孝義, 浅川義範, Wen Liu, 阿部郁朗
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] cryptolactone A及びその誘導体の合成と生物活性評価 (2013)
  • Author(s): 小栗友紀, 稲井誠, 伊藤卓也, 堀川美津代, 加来裕人, 角田鉄人
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] 新規生物活性類縁体の創製を目指した放線菌代謝産物の生合成研究 (2012)
  • Author(s): 伊藤卓也
  • Organizer: 文科省戦略的研究基盤形成支援事業『疾患関連遺伝子及び疾患治療に用いる天然有機化合物の生合成遺伝子の包括的解析』第3回研究発表会
  • Place of Presentation: 徳島文理大学薬学部(徳島)
  • Year and Date: 2012-07-07
• [Presentation] 新規生物活性類縁体の創製を目指した放線菌代謝産物の生合成研究 (2012)
  • Author(s): 伊藤卓也
  • Organizer: 第51回日本薬学会中国四国支部学術大会
  • Place of Presentation: 島根
• [Presentation] Cloning and Characterization of Antimycin Biosynthetic Gene Cluster and Huge PKS Gene Cluster (2012)
  • Author(s): Ito, T,. Awakawa T., Qu, X., Yan, Y., Asakawa, Y., Liu, W., Abe, I.
  • Organizer: International Conference of Natural Products Biosynthesis (ICNPB) Enzymology, Structural Biology, Drug Discovery and Genome Mining
  • Place of Presentation: Awaji Shima, Japan
• [Presentation] Calyculin A生合成遺伝子クラスターの探 (2012)
  • Author(s): 脇本敏幸, 江上蓉子, 淡川孝義, 伊藤卓也, 兼目裕允, 浅川義範, 阿部郁朗
  • Organizer: 第54回天然有機化合物討論会
  • Place of Presentation: 東京
• [Presentation] シンビジウムグレートフラワー'マリーローランサン'の根の化学成分とそれらの抗菌活性について(2) (2012)
  • Author(s): 吉川和子, 井関賀奈子, 伊藤卓也, 浅川義範, 橋本敏弘, 河野幸子
  • Organizer: 日本生薬学会第59回年会
  • Place of Presentation: 千葉
• [Presentation] 新規生物活性類縁体の創製を目指した放線菌代謝産物の生合成研究 (2012)
  • Author(s): 伊藤卓也
  • Organizer: 第 51回日本薬学会中国四国支部学術大会
  • Place of Presentation: 松江
  • Invited
• [Presentation] Cloning and Characterization of Antimycin Biosynthetic Gene Cluster and Huge PKS Gene Cluster (2012)
  • Author(s): Takuya Ito, Takayoshi Awakawa, Xudong Qu, Yan Yan, Yoshinori Asakawa, Wen Liu, Ikuro Abe
  • Organizer: International Conference of Natural Products Biosynthesis
  • Place of Presentation: Awaji-shima
• [Presentation] Calyculin A生合成遺伝子クラスターの探索 (2012)
  • Author(s): 脇本 敏幸、江上 蓉子、淡川 孝義、伊藤 卓也、兼目 裕允、浅川 義範、阿部 郁朗
  • Organizer: 第54回天然有機化合物討論会
  • Place of Presentation: 東京
• [Presentation] シンビジウム グレートフラワー • マリーローランサンの根の化学成分とそれらの抗菌活性について(2) (2012)
  • Author(s): 吉川和子、井関賀奈子、伊藤卓也、浅川義範、橋本敏弘、河野幸子
  • Organizer: 日本生薬学会第59回年会
  • Place of Presentation: 千葉
• [Remarks]
  • URL: http://p.bunri-u.ac.jp/lab01/home.htm
• [Remarks] 徳島文理大学薬学部薬化学研究室
  • URL: http://p.bunri-u.ac.jp/lab01/home.htm
• [Remarks] 文科省戦略的研究基盤形成支援事業 徳島文理大学大学院薬学研究科
  • URL: http://p.bunri-u.ac.jp/lab04/senryaku/index.html