A Desaturase-Like Enzyme Catalyzes Oxazole Formation in Pseudomonas Indolyloxazole Alkaloids
Dr. Alexander O. Brachmann
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorSilke I. Probst
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorJoel Rüthi
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorDarya Dudko
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorProf. Dr. Helge B. Bode
Goethe Universität Frankfurt, Institute of Molecular Biological Science, Max-von-Laue Str. 9, 60438 Frankfurt am Main, Germany
Senckenberg Gesellschaft für Naturforschung, Senckenberganlage 25, 60325 Frankfurt am Main, Germany
Buchmann Institute for Molecular Life Sciences (BMLS), Johann Wolfgang Goethe Universität, Max-von-Laue-Straße 15, 60438 Frankfurt am Main, Germany
Max-Planck-Institute for Terrestrial Microbiology, Department of Natural Products in Organismic Interactions, 35043 Marburg, Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. Jörn Piel
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorDr. Alexander O. Brachmann
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorSilke I. Probst
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorJoel Rüthi
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorDarya Dudko
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorProf. Dr. Helge B. Bode
Goethe Universität Frankfurt, Institute of Molecular Biological Science, Max-von-Laue Str. 9, 60438 Frankfurt am Main, Germany
Senckenberg Gesellschaft für Naturforschung, Senckenberganlage 25, 60325 Frankfurt am Main, Germany
Buchmann Institute for Molecular Life Sciences (BMLS), Johann Wolfgang Goethe Universität, Max-von-Laue-Straße 15, 60438 Frankfurt am Main, Germany
Max-Planck-Institute for Terrestrial Microbiology, Department of Natural Products in Organismic Interactions, 35043 Marburg, Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. Jörn Piel
Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland
Search for more papers by this authorGraphical Abstract
Indolyloxazole alkaloids are widespread natural products with diverse bioactivities but previously unknown biosynthesis. Transposon mutagenesis, heterologous pathway expression, and labeling experiments provide evidence for a Pseudomonas pathway involving oxazole formation by cyclization as a new reaction type catalyzed by a desaturase-like enzyme.
Abstract
Indolyloxazole alkaloids occur in diverse micro- and macroorganisms and exhibit a wide range of pharmacological activities. Despite their ubiquitous occurrence and simple structures, the biosynthetic pathway remained unknown. Here, we used transposon mutagenesis in the labradorin producer Pseudomonas entomophila to identify a cryptic biosynthetic locus encoding an N-acyltransferase and a non-heme diiron desaturase-like enzyme. Heterologous expression in E. coli demonstrates that both enzymes are sufficient to produce indolyloxazoles. Probing their function in stable-isotope feeding experiments, we provide evidence for an unusual desaturase mechanism that generates the oxazole by decarboxylative cyclization.
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