Plasticity of the Malleobactin Pathway and Its Impact on Siderophore Action in Human Pathogenic Bacteria

Chemistry – A European Journal
2015.0

Abstract

<jats:title>Abstract</jats:title><jats:p>The human pathogenic bacteria <jats:italic>Burkholderia mallei</jats:italic>, <jats:italic>Burkholderia pseudomallei</jats:italic>, and <jats:italic>Burkholderia thailandensis</jats:italic> harbor a highly conserved gene cluster coding for the biosynthesis of the long sought‐after malleobactins. Four new, unexpected congeners of the malleobactin family that were isolated and fully characterized in this study feature unusual deviations from the parent, ornibactin‐like architecture. Thus, the malleobactin non‐ribosomal peptide synthetase (NRPS) has a rare flexibility that yields diverse peptide backbones, of which one candidate confers pronounced siderophore activity (EC<jats:sub>50</jats:sub>: 8.4 μ<jats:sc>M</jats:sc>, CAS assay). These findings not only unveil a highly diverse assembly line but also are an important addition to the knowledgebase of the pathogens’ metabolomes.

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