Basics of Fungal Siderophores: Classification, Iron Transport and Storage, Chemistry and Biosynthesis, Application, and More

Arputhanantham, Shyam Sundar; Raja, Kalpana; Shanmugam, Latha; Raman, Vijayakumar

doi:10.1007/978-3-030-53077-8_1

Cited by 1 publication

(1 citation statement)

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“…The low environmental bioavailability of iron in the environment, driven by its propensity to form insoluble ferric (Fe 3+ ) hydroxides, necessitates specific acquisition mechanisms, particularly for pathogens exploiting host iron stores [6,9]. A. fumigatus employs two main iron uptake strategies: low-affinity ferrous (Fe 2+ ) iron and high-affinity ferric iron uptake systems including siderophore-mediated iron acquisition (SIA) and reductive iron assimilation (RIA) [10,11]. Siderophores are low molecular mass, ferric iron-specific chelators [10] and this research focuses on SIA, a key virulence factor during host infection [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Structural and functional characterization of SidF, a possible dual substrateAspergillus fumigatusN5-acetyl-N5-hydroxy-L-ornithine transacetylase

Poonsiri,

Demitri,

Stransky

et al. 2024

Preprint

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Siderophore-mediated iron acquisition is essential for the virulence ofAspergillus fumigatus, a fungus causing life-threatening aspergillosis. Developing drugs targeting the siderophore biosynthetic pathway could help improve disease management. The transacetylases SidF and SidL generate intermediates for different siderophores inA. fumigatus.A. fumigatushas a yet unidentified transacetylase that complements SidL during iron deficiency in SidL-lacking mutants.We present the first X-ray structure of SidF, revealing a conserved two-domain architecture with tetrameric assembly. Importantly, the N-terminal domain contributes to protein solubility and oligomerization, while the C-terminal domain containing the GCN5-related N-acetyltransferase (GNAT) motif is crucial for the enzymatic activity and mediates oligomer formation. Notably, AlphaFold modelling demonstrated structural similarity between SidF and SidL. Enzymatic assays showed that SidF can utilize acetyl-CoA as a donor, previously thought to be a substrate of SidL but not SidF, and selectively uses N5-hydroxy-L-ornithine as an acceptor. Based on these findings, we propose SidF as the unknown transacetylase complementing SidL activity, highlighting its central role inA. fumigatussiderophore biosynthesis.This study elucidates the structure of SidF and reveals a novel role in siderophore biosynthesis. Investigation of this uncharacterized GNAT protein enhances our understanding of fungal virulence and holds promise for its potential application in developing antifungal therapies.

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