Non-canonical two-step biosynthesis of anti-oomycete indole alkaloids in Kickxellales

Fungal Biology and Biotechnology

Research

Veit G. Haensch¹  Christian Hertweck²  Kerstin Voigt³  Caroline Semm³  Sebastian Dörner⁴  Robin Sonnabend⁴  Julia Gressler⁴  Markus Gressler⁴  Johannes Rassbach⁴  Nathalie Hilsberg⁴ 

[1] Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany;Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany;Faculty of Biological Sciences, Institute of Microbiology, Friedrich Schiller University Jena, Neugasse 25, 07743, Jena, Germany;Faculty of Biological Sciences, Institute of Microbiology, Friedrich Schiller University Jena, Neugasse 25, 07743, Jena, Germany;Jena Microbial Resource Collection (JMRC), Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany;Faculty of Biological Sciences, Pharmaceutical Microbiology, Friedrich Schiller University Jena, Winzerlaer Strasse 2, 07745, Jena, Germany;Pharmaceutical Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute, Winzerlaer Strasse 2, 07745, Jena, Germany;

关键词: Early-diverging fungi;    Secondary metabolite;    Indole alkaloid;    Linderina pennispora;    CoA ligase;    Transferase;    Indole-3-acetic acid;   

DOI  :  10.1186/s40694-023-00166-x

 received in 2023-05-30, accepted in 2023-08-06,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundFungi are prolific producers of bioactive small molecules of pharmaceutical or agricultural interest. The secondary metabolism of higher fungi (Dikarya) has been well-investigated which led to > 39,000 described compounds. However, natural product researchers scarcely drew attention to early-diverging fungi (Mucoro- and Zoopagomycota) as they are considered to rarely produce secondary metabolites. Indeed, only 15 compounds have as yet been isolated from the entire phylum of the Zoopagomycota.ResultsHere, we showcase eight species of the order Kickxellales (phylum Zoopagomycota) as potent producers of the indole-3-acetic acid (IAA)-derived compounds lindolins A and B. The compounds are produced both under laboratory conditions and in the natural soil habitat suggesting a specialized ecological function. Indeed, lindolin A is a selective agent against plant-pathogenic oomycetes such as Phytophthora sp. Lindolin biosynthesis was reconstituted in vitro and relies on the activity of two enzymes of dissimilar evolutionary origin: Whilst the IAA–CoA ligase LinA has evolved from fungal 4-coumaryl-CoA synthetases, the subsequently acting IAA-CoA:anthranilate N-indole-3-acetyltransferase LinB is a unique enzyme across all kingdoms of life.ConclusionsThis is the first report on bioactive secondary metabolites in the subphylum Kickxellomycotina and the first evidence for a non-clustered, two-step biosynthetic route of secondary metabolites in early-diverging fungi. Thus, the generally accepted “gene cluster hypothesis” for natural products needs to be reconsidered for early diverging fungi.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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