Generating molecular diversity by the wide range of polyketide synthases

2012 Fiscal Year Final Research Report

• Project/Area Number: 22241054
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: University of Shizuoka
• Principal Investigator: NOGUCHI Hiroshi 静岡県立大学, 薬学部, 教授 (60126141)
• Co-Investigator(Kenkyū-buntansha): 久城 哲夫 明治大学, 農学部, 准教授 (80373299) ; 梅原 薫 静岡県立大学, 薬学部, 講師 (40185070)
• Co-Investigator(Renkei-kenkyūsha): 渡辺 賢二 静岡県立大学, 薬学部, 准教授 (50360938) ; 飯田 滋 静岡県立大学, 生活健康科学研究科・薬学研究科, 特任教授 (30012777)
• Project Period (FY): 2010 – 2012
• Keywords: ゲノム / 酵素工学 / 生理活性 / biosynthesis / 生合成

Research Abstract

Novel type III PKS was isolated from Garcinia mangostana L. , which contains mainly prenylated xanthones. A key prenyltransferase involved in the biosynthesis of abundant fungal meroterpenoids derived from 3,5-dimethylorsellinic was identified. The prenylated product serves as a key intermediate in the biosynthesis of series of meroterpenoids in fungi. With Aspergillus nidlans, Metabolic engineering of yeast for heterologous production of tryprostatins and other compounds was developed through our engineered strain of Saccharomyces cerevisiae, SCKW5. Further trial to architect comprehensive system to form secondary metabolites with Chaetomium globosum is under progress.

Research Products

• [Journal Article] Combinatorial generation of complexity by redox enzymes in the chaetoglobosin a biosynthesis (2013)
  • Author(s): K. Ishiuchi, T. Nakazawa, F. Yagishita, T. Mino, H. Noguchi, K. Hotta, K. Watanabe
  • Journal Title: J. Am. Chem. Soc Volume: 135 Pages: 7371-7377
• [Journal Article] Terretonin biosynthesis requires methylation as essential step for cyclization (2012)
  • Author(s): Y. Matsuda, T. Awakawa, T. Itoh, T. Wakimoto, T. Kushiro, I. Fujii, Y. Ebizuka, I. Abe
  • Journal Title: ChemBioChem Volume: 13(12) Pages: 1738-1741
• [Journal Article] Identification of a key prenyltransferase involved in biosynthesis of the most abundant fungal meroterpenoids derived from 3,5-dimethylorsellinic acid (2012)
  • Author(s): T. Itoh, K. Tokunaga, E.K. Radhakrishnan, I. Fujii, I. Abe, Y. Ebizuka, T. Kushiro
  • Journal Title: ChemBioChem Volume: 13(8) Pages: 1132-1135
• [Journal Article] Benzophenone synthase from Garcinia mangostana (2012)
  • Author(s): N. Nualkaew, H. Morita, Y. Shimokawa, K. Kinjo, T. Kushiro, W. De-Eknamkul, Y. Ebizuka, I. Abe
  • Journal Title: L. pericarps. Phytochemistry Volume: 77 Pages: 60-69
• [Journal Article] Molecular cloning and characterization of copper amine oxidase from Huperzia serrate (2012)
  • Author(s): J. Sun, H. Morita, G. Chen, H. Noguchi, I.Abe
  • Journal Title: Bioorg. & Med. Chem. Lettr. Volume: 22(18) Pages: 5784-5790
• [Journal Article] Induced production of mycotoxins in an endophytic fungus from the medicinal plant Datura stramonium L. (2012)
  • Author(s): J. Sun, T. Awakawa, H. Noguchi, I. Abe
  • Journal Title: Bioorg. & Med. Chem.Lettr Volume: 22(20) Pages: 6397-6400
• [Journal Article] Prenylation of a Nonaromatic Carbon of Indolylbutenone by a Fungal Indole Prenyltransferase (2012)
  • Author(s): J. Chen, H. Morita, T. Wakimoto, T. Mori, H. Noguchi, I. Abe
  • Journal Title: Organic Letters Volume: 14 (12) Pages: 3080-3083
• [Journal Article] Establishing a new methodology for genome mining and biosynthesis of polyketides and peptides through yeast molecular genetics (2012)
  • Author(s): K. Ishiuchi, T. Nakazawa, T. Ookuma, S. Sugimoto, M. Sato, Y. Tsunematsu, N. Ishikawa, H. Noguchi, K. Hotta, H. Moriya, K. Watanabe
  • Journal Title: ChemBioChem Volume: 13(6) Pages: 846-854
• [Journal Article] Overexpressing transcriptional regulator in Aspergillus oryzae activates a silent biosynthetic pathway to produce novel polyketide (2012)
  • Author(s): T. Nakazawa, K. Ishiuchi, A. Praseuth, H. Noguchi, K. Hotta, K. Watanabe
  • Journal Title: ChemBioChem Volume: 13(6) Pages: 855-861
• [Journal Article] Overexpressing transcriptional regulator in Chaetomium globosum activates a silent biosynthetic pathway: evaluation of shanorellin biosynthesis (2012)
  • Author(s): Y. Tsunematsu, S. Ichinoseki, T. Nakazawa, N. Ishikawa, H. Noguchi, K. Hotta, K. Watanabe
  • Journal Title: J. of Antibiotics Volume: 65(7) Pages: 377-380
• [Journal Article] Expression, purification and crystallization of an indole prenyltransferase from Aspergillus fumigatus (2012)
  • Author(s): J. Chen, H. Morita, R. Kato, H. Noguchi, S. Sugio, I. Abe
  • Journal Title: Acta Cryst. Section F Volume: 68 Pages: 355-358
• [Journal Article] A comprehensive overview on genomically directed assembly of aromatic polyketides and macrolide lactones using fungal megasynthases (2011)
  • Author(s): T. Saruwatari, A. P Praseuth, M. Sato, K. Torikai, H. Noguchi, K. Watanabe
  • Journal Title: The Journal of Antibiotics Volume: 64 Pages: 9-17
• [Journal Article] Practical Synthesis of dopa derivative for biosynthetic production of potent antitumor natural products, Saframycins and Ecteinascidin 743 (2011)
  • Author(s): K. Torikai, T. Saruwatari, T. Kitano, T. Sano, A. Nakane, H. Noguchi, K. Watanabe
  • Journal Title: Letters In Organic Chemistry Volume: 8-10 Pages: 686-689
• [Journal Article] Enzymatic formation of an aromatic dodecaketide by engineered plant polyketide synthase (2011)
  • Author(s): K. Wanibuchi, H. Morita, H. Noguchi, I. Abe
  • Journal Title: Bioorganic and Medicinal Chemistry Letters Volume: 21 Pages: 2083-2086
• [Journal Article] A struture-based mechanism fior benzalacetone synthase from Rheum palmatum (2010)
  • Author(s): H. Morita, Y . Shimmokawa, M. Tanio, R.Kato, H. Noguchi, S. Sugio, T. Kohno, I. Abe
  • Journal Title: Proc. Nat. Acad. Sci. USA Volume: 107 Pages: 669-673
• [Journal Article] Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpenecyclases (2010)
  • Author(s): T. Itoh, K. Tokunaga, Y. Matsuda, I. Fujii, I. Abe, Y. Ebizuka, T. Kushiro
  • Journal Title: Nature Chemistry Volume: 2 Pages: 858-864
• [Presentation] Functional reconstitution of the saframycin biosynthetic enzymes (2012)
  • Author(s): K. Watanabe
  • Organizer: RCIS International Conference
  • Place of Presentation: Okayama
  • Year and Date: 20121120-21
• [Presentation] Establishing a new methodology for genome mining and biosynthesis of natural products through fungal molecular genomics (2012)
  • Author(s): H. Noguchi
  • Organizer: International Congress on Natural Products Research
  • Place of Presentation: New York, (US)
  • Year and Date: 20120728-0801
• [Presentation] Biologically active molecules from fungi (2012)
  • Author(s): Kenji Watanabe
  • Organizer: 第8回天然物生合成日米セミナー
  • Place of Presentation: 淡路
  • Year and Date: 20120617-22
• [Presentation] A novel triterpene synthase gene from a monocot plant, Imperata cylindrical (2012)
  • Author(s): Tetsuo Kushiro
  • Organizer: The 8thInternational Conference of Natural Product Biosynthesis
  • Place of Presentation: Awaji Yumebutai, Hyogo, Japan
  • Year and Date: 20120617-22
• [Presentation] Biosynthesis of natural products through a fungal molecular genetics (2012)
  • Author(s): T. Nakazawa, T. Ookuma, S. Sugimoto, S. Ichinoseki, Y. Gotanda, N. Ishikawa, Y. Tsunematsu, K. Ishiuchi, H. Noguchi, K. Watanabe
  • Organizer: Philipps-Universitat Marburg
  • Place of Presentation: Germany
  • Year and Date: 20120330-0402
• [Presentation] T. Nakazawa, K. Ishiuchi, K. Hotta, H.Noguchi, H. Moriya, K. Watanabe (2011)
  • Author(s): T. Nakazawa, K. Ishiuchi, K. Hotta, H.Noguchi, H. Moriya, K. Watanabe
  • Organizer: 8th AFMC International Medicinal Chemistry Symposium "Frontier of Medicinal Science"
  • Place of Presentation: KEIO PLAZA HOTEL TOKYO(東京)
  • Year and Date: 2011-11-29
• [Presentation] Yeast, a more manageable non-ribosomal peptide mill for Spirotryprostatin B assembly. (2011)
  • Author(s): K. Watanabe
  • Organizer: International Union of Microbiological Societies 2011 Congress, Sapporo Convention Center
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-06
• [Presentation] Yeast, a more manageable non-ribosomal peptide mill for Spirotryprostatin B assembly (2011)
  • Author(s): K. Watanabe
  • Organizer: 11th European Conference on Fungal Genetics. Society for Industrial Microbiology, Annual meeting and exhibition 2011
  • Place of Presentation: Sheraton New Orleans, New Orleans (LA)
  • Year and Date: 2011-07-24
• [Presentation] Combinatorial biosynthesis of unnatural novel prenylated alkaloids. Abstrac (2010)
  • Author(s): J. Chen, H. Noguchi
  • Organizer: 2010 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu (HW US)
  • Year and Date: 2010-12-17
• [Presentation] A chemical library by engineered plant polyketide synthase (2010)
  • Author(s): H. Noguchi
  • Organizer: The 1st Current Drug Development International Conference
  • Place of Presentation: Phuket (Thailand)
  • Year and Date: 2010-05-07