{
  "abstract": "Siderophore-mediated iron acquisition is essential for fungal survival, particularly under iron-limiting conditions. In Aspergillus fumigatus, SidG, a member of the GCN5-related N-acetyltransferase (GNAT) superfamily, catalyses the final step in the biosynthesis of the extracellular siderophore triacetylfusarinine C (TAFC) through sequential acetylation of the precursor fusarinine C (FsC). However, the timing, catalytic mechanism, and functional significance of this modification are not fully understood. Here, we reconstituted SidG activity in vitro and combined native mass spectrometry, X-ray crystallography, molecular dynamics simulations, and site-directed mutagenesis to investigate its catalytic properties. Our analyses demonstrate that SidG selectively binds acetyl-CoA from the cellular milieu and iteratively acetylates the FsC scaffold prior to iron chelation. Structural, biochemical, and molecular dynamics analyses support a direct transfer mechanism, identify key catalytic residues, and demonstrate the strict selectivity of SidG for short-chain acyl-CoA donors. Together, these findings establish the molecular basis for SidG-dependent siderophore tailoring and expand our understanding of GNAT-catalysed transformations in fungal natural product biosynthesis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "J. D. Newman"
    },
    {
      "name": "Y. T. C. Ho"
    },
    {
      "name": "C. D. Fage"
    },
    {
      "name": "G. Winkelmann"
    },
    {
      "name": "L. M. Alkhalaf"
    },
    {
      "name": "J. R. Lewandowski"
    },
    {
      "name": "F. Alberti"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Jenner"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4erezebg9p1n4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754016",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754016v1.full",
  "id": "4erezebg9p1n4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754016v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "2736|Microbial Natural Products and Biosynthesis"
    ]
  ],
  "openalex": "W7212714202",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754016v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4erezebg9p1n4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:46Z",
      "native_id": "10.64898/2026.09.24.754016",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754016v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Microbial Natural Products and Biosynthesis",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Structural and biochemical characterisation of an iterative GCN5-related N-acetyltransferase required for fungal siderophore tailoring",
  "title_text": "Structural and biochemical characterisation of an iterative GCN5-related N-acetyltransferase required for fungal siderophore tailoring",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:46Z",
  "url": "https://research.draconitic.com/paper/4erezebg9p1n4",
  "venue": "bioRxiv",
  "versions": []
}