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Pyonitrins A-D: Chimeric Natural Products Produced by Pseudomonas protegens.

ABSTRACT: 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.

SUBMITTER: Mevers E

PROVIDER: S-EPMC6823628 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Pyonitrins A-D: Chimeric Natural Products Produced by Pseudomonas protegens.

Mevers Emily E Saurí Josep J Helfrich Eric J N EJN Henke Matthew M Barns Kenneth J KJ Bugni Tim S TS Andes David D Currie Cameron R CR Clardy Jon J

Journal of the American Chemical Society 20191016 43

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 ...[more]

PMID: 31600443

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Pyonitrins A-D: Chimeric Natural Products Produced by Pseudomonas protegens.

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Pyonitrins A-D: Chimeric Natural Products Produced by <i>Pseudomonas protegens</i>.

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