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

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)737-743
Number of pages7
JournalNature Chemistry
Volume7
Issue number9
DOIs
Publication statusPublished - 2015 Sep 22

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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