The authors report a newly identified cyanobacterial siderophore, cyanochelin C, discovered and characterized from cyanobacterial material. Siderophores are high-affinity iron-chelating molecules that many microorganisms produce to solubilize and acquire iron, an essential but often limiting micronutrient in aquatic and terrestrial ecosystems. Cyanobacteria, as photosynthetic prokaryotes central to global primary production, require iron for core metabolic enzymes; however, relatively few cyanobacterial siderophores have been described to date. The identification of cyanochelin C therefore addresses a notable gap in the known chemical diversity of cyanobacterial iron-acquisition systems.
The molecular structure and stereochemistry of cyanochelin C were elucidated using extensive nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses reported by the authors. These spectroscopic data support the assignment of the molecule’s composition and the specific placement of chelating residues. A defining structural feature is the presence of two β-hydroxyaspartate residues that serve as the iron-coordinating ligands. The combined NMR and MS evidence was used to establish both connectivity and stereochemical aspects of the siderophore, as described in the preprint.
Alongside chemical characterization, the study identifies the corresponding biosynthetic gene cluster (BGC) predicted to encode the enzymes and assembly machinery required for cyanochelin C production. The BGC discovery links the molecular structure to a genetic locus in cyanobacteria, enabling further study of biosynthesis, regulation, and distribution among cyanobacterial lineages.
Bioinformatic interrogation of the identified BGC revealed an acylase enzyme, designated CcsQ, that clusters with a broader cyanobacteria-specific family of acylases. This family was observed to be associated with other predicted siderophore-encoding BGCs in cyanobacteria, suggesting a recurring genomic association between this acylase class and siderophore pathways. The genomic context and sequence relationships indicate that CcsQ belongs to a lineage of acyl hydrolases that may be specialized for modifications of cyanobacterial secondary metabolites, including siderophores.
The authors report deacylation of the siderophore by CcsQ, indicating that this acylase acts on the cyanochelin scaffold to remove an acyl group. This enzymatic activity expands understanding of post-synthetic modifications in cyanobacterial siderophore biosynthesis and maturation. The observation ties the biochemical transformation to a specific enzyme encoded within the BGC and supports a model in which acylation and subsequent acyl-hydrolysis contribute to siderophore structural diversity or activation.
Discovery of cyanochelin C and its enzymatic deacylation by CcsQ broaden the known structural repertoire of cyanobacterial siderophores and illuminate an enzymatic reaction important for their processing. Identification of a cyanobacteria-specific acylase family associated with siderophore BGCs suggests conserved or recurrent biochemical strategies in cyanobacterial iron acquisition pathways. These findings provide a foundation for future biochemical, ecological, and evolutionary studies to determine how widespread cyanochelin-type siderophores are, how acylation/deacylation affects siderophore function, and how these pathways impact cyanobacterial physiology and interactions in iron-limited environments.
This work is presented as a preprint on bioRxiv and has not been peer reviewed. The preprint was posted July 25, 2026. Authors listed include Viviana Di Matteo, Lenka Marešová Štenclová, Berness Peter Falcao, Pavel Hrouzek, Petra Urajová, Jan Mareš, Germana Esposito, Alfonso Mangoni, Valeria Costantino, and Tomáš Galica, with correspondence contact provided for Tomáš Galica. Declared funding sources include the Czech Science Foundation, University of South Bohemia, the Ministry of Education Youth and Sports (CZ.02.01.01/00/22_008/0004624), the Italian Ministry of University and Research, and institutional support from Università degli Studi di Napoli Federico II. The authors declared no competing interests.
Note: Detailed experimental methods, full spectral data, and supplementary material were referenced in the preprint; specific experimental parameters and data points are available in the article’s supplementary files but are not reproduced here beyond the summary provided in the source.