P-22 エピジェネティクスを制御する化学修飾酵素阻害剤を用いた多様な糸状菌ポリケチドの創生(ポスター発表の部)

• 浅井 禎吾

  東北大院薬

• 山本 崇史

  東北大院薬

• 森田 峻太郎

  東北大院薬

• 白田 直樹

  東北大院薬

• 大島 吉輝

  東北大院薬

書誌事項

タイトル別名

• P-22 Production of Structurally Diverse Fungal Polyketides Using Small Molecular Epigenetic Modifiers(Poster Presentation)

抄録

Filamentous fungi are well-known producers of a large number of diverse natural products, many of which have fascinating structures and important biological activities that have attracted the attention of natural product chemists, organic chemists, and pharmacologists. As fungal genomes have been sequenced, it has become clear that there are far more secondary metabolite-encoding biosynthetic gene clusters than were evident in previous chemical studies. This suggests that fungi have dozens of unique gene cluster coding for uncharacterized polyketides and nonribosomal peptides. Many of these gene clusters are said to be transcriptionally suppressed under standard laboratory culture conditions. Recently, it was demonstrated that epigenetic modification compounds, such as histone deacetylase (HDAC) inhibitors or DNA methyltransferase inhibitors, could induce transcriptional up-regulation of many PKS and NRPS-encoding gene clusters in a model fungus, Aspergillus niger. In an effort to obtain novel bioactive polyketides, we applied these chemicals to cultures of Chaetomium species. Cultivation in the presence of suberoyl bis-hydroxamic acid (SBHA) (Zn^<2+> type HDAC inhibitor), followed by extraction, resulted in the isolation of novel prenylated polyketides 1-11 from Chaetomium indicum. Among the compounds, 9-11 possessed unprecedented polycyclic polyketide frameworks possibly generated via a [4+2] cycloaddition. On the other hands, addition of nicotinamide (a NAD^+ dependent HDAC inhibitor) to the culture medium of C. mollipilium significantly enhanced a series of C_<13>-polyketides production and led to the isolation of five novel C_<13>-polyketides (12-16) along with (-)-aureonitol and spiroketal 17. The structures of 1-17 with absolute stereochemistries were elucidated by spectroscopic analysis, vibrational circular dichroism (VCD), X-ray single crystal diffraction studies, and chemical trans formations and we describe plausible biosynthetic pathways to account for their biosynthetic relationship. This study suggested that both types of HDAC inhibitors are useful to obtain diverse fungal polyketides via activation of silent biosynthetic pathways.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 54 (0), 525-530, 2012

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390001206079543936
• NII論文ID: 110010013881
• DOI: 10.24496/tennenyuki.54.0_525
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可