Genome mining approach for harnessing the cryptic gene cluster in Alternaria solani: production of PKS–NRPS hybrid metabolite, didymellamide B. Issue 25 (22nd June 2016)

• Record Type: Journal Article
• Authors: Ugai, Takahiro; Minami, Atsushi; Gomi, Katsuya; Oikawa, Hideaki
• Is Part Of: Tetrahedron letters. Volume 57:Issue 25(2016)
• Page Start: 2793
• Page End: 2796
• Publication Date: 2016-06-22
• Subjects: Polyketide synthase -- Didymellamide -- Natural product biosynthesis -- Heterologous expression -- Fungi; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.05.043
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Heterologous production of fungal metabolite with 3 genes. Biosynthetic gene dependent production of fungal polyketide. Non-enzymatic [4+2] cycloaddition of highly reactive linear triene. endo -Selective Diels–Alder reaction generating trans -decalin with 2-pyridone. Abstract: Using a heterologous expression system in Aspergillus oryzae we characterized cryptic biosynthetic genes found in Alternaria solani . This system enabled the isolation of an antifungal metabolite, didymellamide B, which was previously not detected in the extract of the A. solani . The co-production and chemical transformation of didymellamide congeners enabled us to decipher the biosynthetic pathway of didymellamide B as follows: (1) formation of a linear polyketide chain with 3-acyltetramate, (2) oxidative ring expansion to yield a 2-pyridone skeleton, and (3) non-enzymatic endo -selective [4+2] cycloaddition to afford a trans -decalin. These results demonstrate the robustness and reliability of the A. oryzae expression system.