Frankobactin Metallophores Produced by Nitrogen-Fixing Frankia Actinobacteria Function in Toxic Metal Sequestration

A series of new metallophores, referred to as frankobactins, were extracted from cultures of the symbiotic and nitrogen-fixing actinobacterium Frankia sp. CH37. Structure elucidation revealed a 2-hydroxyphenyl-substituted oxazoline core and a chain composed of five proteinogenic and nonproteinogenic amino acids, suggesting nonribosomal peptide synthesis as the biosynthetic origin. By whole-genome sequencing, bioinformatic analysis, and comparison with other Frankia strains, the genetic locus responsible for the biosynthesis was detected. Spectrophotometric titration of frankobactin with Fe(III) and Cu(II) and mass spectrometry established the 1:1 (metal:frankobactin) coordination. Uptake experiments suggested that frankobactin A(1) (1) did not serve to recruit iron, but to detoxify Cu(II). As frankobactin A(1) prevents the cellular entry of Cu(II), it could play a crucial role in the symbiosis of Frankia sp. and its host in the reclamation of copper-contaminated soil.

Automated summary

A new series of metallophores called frankobactins was extracted from the symbiotic actinobacterium Frankia sp. CH37, with structure elucidation revealing its biosynthetic origin and coordination with Fe(III) and Cu(II). The genetic locus responsible for biosynthesis was identified through genomic sequencing and bioinformatic analysis, and uptake experiments indicated a possible role of frankobactins in detoxifying Cu(II) during symbiosis between Frankia sp. and its host.