A Desaturase-Like Enzyme Catalyzes Oxazole Formation in Pseudomonas Indolyloxazole Alkaloids.

Autor: Brachmann AO; Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland., Probst SI; Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland., Rüthi J; Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland., Dudko D; Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland., Bode HB; 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., Piel J; Eidgenössische Technische Hochschule (ETH) Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Apr 12; Vol. 60 (16), pp. 8781-8785. Date of Electronic Publication: 2021 Mar 05.
DOI: 10.1002/anie.202014491
Abstrakt: 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.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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