Biosynthesis of Peptide Siderophores in Actinobacteria

Actinobacteria, notably genera such as Streptomyces and Corynebacterium, deploy peptide siderophores to scavenge ferric iron under conditions of scarcity. These iron-chelating natural products typically feature hydroxamate or catecholate moieties assembled by non-ribosomal peptide synthetases (NRPSs). Modular NRPS enzymes orchestrate the selection, activation and condensation of amino acids—including modified ornithine and dihydroxybenzoate units—into linear or cyclic peptides. Tailoring enzymes, such as flavin-dependent monooxygenases and N-acetyltransferases, introduce hydroxylations and acyl decorations that modulate affinity and specificity for iron. Biosynthetic gene clusters (BGCs) encode NRPS modules, accessory tailoring proteins and dedicated transporters, often organised in conserved operons. Genetic redundancy and environmental cues, notably iron concentration, can direct a single cluster to yield structurally distinct metabolites. The resulting siderophores play crucial roles in microbial competition, symbiosis with plants and animals, and pathogenesis. Deciphering their biosynthesis enables pathway engineering for novel iron-chelators and Trojan-horse antibiotics, with broad implications for biotechnology and medicine.

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Biosynthesis of Peptide Siderophores in Actinobacteria publication trend

The graph below shows the total number of articles in biosynthesis of peptide siderophores in actinobacteria across all publications each year (not limited to Nature Index journals).

Technical terms

Siderophore: A small, high-affinity iron-chelating compound secreted by microorganisms to sequester ferric iron from the environment.

Non-ribosomal peptide synthetase (NRPS): A large, modular enzyme that assembles peptides independently of the ribosome, selecting, activating and condensing amino acids into specific sequences.

Biosynthetic gene cluster (BGC): A contiguous set of co-regulated genes encoding the enzymes and transporters required for the full biosynthesis of a specialised metabolite.

Ferrichrome: A cyclic hexapeptide hydroxamate siderophore formed by three N5-acetyl-N5-hydroxyornithine residues and three glycine or serine units, common in fungi and some Actinobacteria.

Hydroxamate: A functional group (R-CON(R’)-O-) derived from hydroxamic acid, important for coordinating ferric iron in many siderophores.

References

1. Elucidation of the ferrichrome siderophore biosynthetic pathway in albomycin-producing Streptomyces sp. ATCC 700974. Journal of Biological Chemistry (2023).
2. A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators. mBio (2019).
3. Biosynthesis and Chemical Synthesis of Albomycin Nucleoside Antibiotics. Antibiotics (2022).