Use of a biosynthetic intermediate to explore the chemical diversity of pseudo-natural fungal polyketides

Teigo Asai, Kento Tsukada, Satomi Ise, Naoki Shirata, Makoto Hashimoto, Isao Fujii, Katsuya Gomi, Kosuke Nakagawara, Eiichi N. Kodama, Yoshiteru Oshima

研究成果: Article査読

52 被引用数 (Scopus)

抄録

The structural complexity and diversity of natural products make them attractive sources for potential drug discovery, with their characteristics being derived from the multi-step combination of enzymatic and non-enzymatic conversions of intermediates in each biosynthetic pathway. Intermediates that exhibit multipotent behaviour have great potential for use as starting points in diversity-oriented synthesis. Inspired by the biosynthetic pathways that form complex metabolites from simple intermediates, we developed a semi-synthetic process that combines heterologous biosynthesis and artificial diversification. The heterologous biosynthesis of fungal polyketide intermediates led to the isolation of novel oligomers and provided evidence for ortho-quinonemethide equivalency in their isochromene form. The intrinsic reactivity of the isochromene polyketide enabled us to access various new chemical entities by modifying and remodelling the polyketide core and through coupling with indole molecules. We thus succeeded in generating exceptionally diverse pseudo-natural polyketides through this process and demonstrated an advanced method of using biosynthetic intermediates.

本文言語English
ページ(範囲)737-743
ページ数7
ジャーナルNature Chemistry
7
9
DOI
出版ステータスPublished - 2015 9 22

ASJC Scopus subject areas

  • 化学 (全般)
  • 化学工学(全般)

フィンガープリント

「Use of a biosynthetic intermediate to explore the chemical diversity of pseudo-natural fungal polyketides」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル