Non-canonical two-step biosynthesis of anti-oomycete indole alkaloids in Kickxellales
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Published:2023-09-05
Issue:1
Volume:10
Page:
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ISSN:2054-3085
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Container-title:Fungal Biology and Biotechnology
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language:en
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Short-container-title:Fungal Biol Biotechnol
Author:
Rassbach Johannes,Hilsberg Nathalie,Haensch Veit G.,Dörner Sebastian,Gressler Julia,Sonnabend Robin,Semm Caroline,Voigt Kerstin,Hertweck Christian,Gressler Markus
Abstract
Abstract
Background
Fungi 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.
Results
Here, 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.
Conclusions
This 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.
Funder
Deutsche Forschungsgemeinschaft Friedrich-Schiller-Universität Jena
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,Applied Microbiology and Biotechnology,Ecology, Evolution, Behavior and Systematics,Biotechnology
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