Structural and Functional Siderophore Remodeling by Enzymatic Delipidation.
TL;DR
It is revealed that Pandoraea species, including environmental isolates and opportunistic pathogens typically acquired from the environment, produce bifunctional lipopeptides that undergo enzymatic remodeling to switch from promoting bacterial motility to optimizing iron capture.
Abstract
Bacteria employ specialized metabolites called siderophores to acquire scarce iron, but these molecules may serve additional ecological roles. Here, we reveal that Pandoraea species, including environmental isolates and opportunistic pathogens typically acquired from the environment, produce bifunctional lipopeptides that undergo enzymatic remodeling to switch from promoting bacterial motility to optimizing iron capture. Through genome mining and metabolic profiling, we discovered pandorachelins, diazeniumdiolate-containing siderophores. Comprehensive NMR analysis, derivatization, and isotope labeling established that pandorachelin A is a head-to-tail-fused homodetic cyclopeptide, revising a recently proposed structure. We identified the elusive biosynthetic precursor, pandorachelin B, as a lipocyclopeptide with a lactone moiety and N-terminal fatty acid. A specialized acylase (PdnM) cleaves the lipid tail of pandorachelin B, triggering an O→N acyl shift that contracts the ring and transforms the biological function: the lipopeptide enables bacterial swarming through surfactant activity, while the delipidated product exhibits enhanced iron-chelating capacity but no motility promotion. Genetic knockouts, enzyme reconstitution, and phenotypic assays confirm this maturation sequence. The functional switch correlates with ecological niche across Pandoraea species, revealing a sophisticated strategy for niche colonization and nutrient acquisition. These findings identify PdnM as a potential antivirulence target and expand the functional repertoire of bacterial siderophores.