Ecological Niche-Inspired Genome Mining Leads to the Discovery of Crop-Protecting Nonribosomal Lipopeptides Featuring a Transient Amino Acid Building Block.

Autor:	Götze S; Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Vij R; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Burow K; Research Centre for Horticultural Crops (FGK), Fachhochschule Erfurt, Kühnhäuser Straße 101, 99090 Erfurt, Germany., Thome N; Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Urbat L; Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Schlosser N; Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Pflanze S; Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Müller R; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Hänsch VG; Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Schlabach K; Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Fazlikhani L; Research Centre for Horticultural Crops (FGK), Fachhochschule Erfurt, Kühnhäuser Straße 101, 99090 Erfurt, Germany., Walther G; National Reference Center for Invasive Fungal Infections, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Dahse HM; Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Regestein L; Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Brunke S; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Hube B; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Hertweck C; Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany., Franken P; Research Centre for Horticultural Crops (FGK), Fachhochschule Erfurt, Kühnhäuser Straße 101, 99090 Erfurt, Germany.; Molecular Phytopathology, Friedrich Schiller University, 07745 Jena, Germany., Stallforth P; Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany.; Faculty of Chemistry and Earth Sciences, Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena, Humboldtstraße 10, 07743 Jena, Germany.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2023 Feb 01; Vol. 145 (4), pp. 2342-2353. Date of Electronic Publication: 2023 Jan 20.
DOI:	10.1021/jacs.2c11107
Abstrakt:	Investigating the ecological context of microbial predator-prey interactions enables the identification of microorganisms, which produce multiple secondary metabolites to evade predation or to kill the predator. In addition, genome mining combined with molecular biology methods can be used to identify further biosynthetic gene clusters that yield new antimicrobials to fight the antimicrobial crisis. In contrast, classical screening-based approaches have limitations since they do not aim to unlock the entire biosynthetic potential of a given organism. Here, we describe the genomics-based identification of keanumycins A-C. These nonribosomal peptides enable bacteria of the genus Pseudomonas to evade amoebal predation. While being amoebicidal at a nanomolar level, these compounds also exhibit a strong antimycotic activity in particular against the devastating plant pathogen Botrytis cinerea and they drastically inhibit the infection of Hydrangea macrophylla leaves using only supernatants of Pseudomonas cultures. The structures of the keanumycins were fully elucidated through a combination of nuclear magnetic resonance, tandem mass spectrometry, and degradation experiments revealing an unprecedented terminal imine motif in keanumycin C extending the family of nonribosomal amino acids by a highly reactive building block. In addition, chemical synthesis unveiled the absolute configuration of the unusual dihydroxylated fatty acid of keanumycin A, which has not yet been reported for this lipodepsipeptide class. Finally, a detailed genome-wide microarray analysis of Candida albicans exposed to keanumycin A shed light on the mode-of-action of this potential natural product lead, which will aid the development of new pharmaceutical and agrochemical antifungals.
Databáze:	MEDLINE
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