Pyonitrins A–D: Chimeric Natural Products Produced by Pseudomonas protegens
| Autor: | Jon Clardy, Kenneth J. Barns, Cameron R. Currie, Tim S. Bugni, David R. Andes, Emily Mevers, Eric J. N. Helfrich, Josep Saurí, Matthew T. Henke |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Antifungal Agents
Magnetic Resonance Spectroscopy Drug Evaluation Preclinical 010402 general chemistry 01 natural sciences Biochemistry Genome Catalysis Pseudomonas protegens chemistry.chemical_compound Mice Colloid and Surface Chemistry Biosynthesis Bacterial Proteins Phenols In vivo Pseudomonas Candida albicans Animals Gene Chromatography High Pressure Liquid Biological Products biology Molecular Structure Communication Candidiasis General Chemistry biology.organism_classification Small molecule 0104 chemical sciences Biosynthetic Pathways Pyrrolnitrin Thiazoles chemistry |
| Zdroj: | Journal of the American Chemical Society |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Bacterial symbionts frequently provide chemical defenses for their hosts, and such systems can provide discovery pathways to new antifungals and structurally intriguing metabolites. This report describes a small family of naturally occurring small molecules with chimeric structures and a mixed biosynthesis that features an unexpected but key nonenzymatic step. An insect-associated Pseudomonas protegens strain's activity in an in vivo murine candidiasis assay led to the discovery of a family of highly hydrogen-deficient metabolites. Bioactivity- and mass-guided fractionation led to the pyonitrins, highly complex aromatic metabolites in which 10 of the 20 carbons are quaternary, and 7 of them are contiguous. The P. protegens genome revealed that the production of the pyonitrins is the result of a spontaneous reaction between biosynthetic intermediates of two well-studied Pseudomonas metabolites, pyochelin and pyrrolnitrin. The combined discovery of the pyonitrins and identification of the responsible biosynthetic gene clusters revealed an unexpected biosynthetic route that would have prevented the discovery of these metabolites by bioinformatic analysis alone. |
| Databáze: | OpenAIRE |
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