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Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.

ABSTRACT: Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere.

SUBMITTER: Steele AD

PROVIDER: S-EPMC5084090 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.

Steele Andrew D AD Steele Andrew D AD Keohane Colleen E CE Knouse Kyle W KW Rossiter Sean E SE Williams Sierra J SJ Wuest William M WM

Journal of the American Chemical Society 20160428 18

Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted ...[more]

PMID: 27096543

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