19 Biosynthesis of mycotoxin verruculogen in the human pathogen Aspergillus fumigatus(Oral Presentation)

• Suzuki Hirokazu

  Chemical Biology Department, Advanced Science Institute, RIKEN

• Kato Naoki

  Chemical Biology Department, Advanced Science Institute, RIKEN

• Takagi Hiroshi

  Chemical Biology Department, Advanced Science Institute, RIKEN

• Uramoto Masakazu

  Chemical Biology Department, Advanced Science Institute, RIKEN

• Usui Takeo

  Graduate School of Life and Environmental Sciences, University of Tsukuba

• Takahashi Shunji

  Chemical Biology Department, Advanced Science Institute, RIKEN

• Sugimoto Yoshikazu

  Division of Chemotherapy, Faculty of Pharmacy, Keio University

• Osada Hiroyuki

  Chemical Biology Department, Advanced Science Institute, RIKEN

Bibliographic Information

Other Title

• 19 真菌毒verruculogenの全生合成経路の解明(口頭発表の部)

Abstract

Aspergillus fumigatus, a ubiquitous saprophytic fungus, is a potentially deadly pathogen that causes invasive aspergillosis in immunocompromised individuals. Some studies have indicated a relationship between the secondary metabolites of A. fumigatus and its virulence; therefore an understanding of mycotoxin biosynthesis will shed light on aspergillosis therapy as well as basic biology regarding its pathogenicity. Here, we present a comprehensive characterization of the ftm gene cluster of A. fumigatus with the aim of elucidating the secondary metabolites that arise from the gene cluster and their biosynthesis. Although it has been suggested that the ftm cluster is involved in the biosynthesis of diketopiperazine mycotoxins, such as fumitremorgins and tryprostatins, the biosynthesis that is based on the ftm cluster is mostly obscure. The main points of our study outcomes are as follows: (i) We elucidated all the secondary metabolites that arise from the ftm cluster, including a tremorgenic mycotoxin, verruculogen. (ii) We revealed that the ftm genes direct the biosynthesis of verruculogen through eight steps. Verruculogen was isolated as a tremorgenic mycotoxin in the 1970s and contains the unique epidioxy-bridge in the structure. (iii) We discovered the novel enzyme FtmF. This enzyme catalyzes the final step in the verruculogen biosynthesis, i.e., epidioxy formation of fumitremorgin B. (iv) We collected the natural products of the verruculogen biosynthesis and characterized its breast cancer resistance protein inhibitory activity.

Journal

• Symposium on the Chemistry of Natural Products, symposium papers

  Symposium on the Chemistry of Natural Products, symposium papers 50 (0), 137-142, 2008

  Symposium on the Chemistry of Natural Products Steering Committee

Details

• CRID: 1390282681055377408
• NII Article ID: 110007066764
• DOI: 10.24496/tennenyuki.50.0_137
• ISSN: 24331856
• Text Lang: ja
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed