{
  "abstract": "Glycyl radical enzymes (GREs) catalyze challenging chemical reactions using a post-translationally installed glycyl radical cofactor. One such enzyme, indoleacetate decarboxylase (IAD), performs the radical-based decarboxylation of indole-3-acetate (I3A) to form the malodorant molecule skatole. In addition to being an odor nuisance, skatole is a human and livestock lung toxin, a suspected carcinogen, and a mosquito attractant, all of which impact human health, agriculture, food production, and wastewater treatment. Here, we use cryogenic electron microscopy to solve a 2.45-[A] resolution structure of indoleacetate decarboxylase from the gut bacterium Olsenella uli. We observe IAD in a homotetrameric form with the substrate I3A bound in all four protomers. The positioning of I3A in the active site is unexpected and is more consistent with a Kolbe-type decarboxylation mechanism, i.e. a decarboxylation initiated by a 1-electron oxidation of the carboxylate moiety rather than being initiated by hydrogen atom transfer (HAT). Previously, a high deuterium content in skatole from IAD assays in D2O was used to support a HAT mechanism over a Kolbe-type mechanism. However, we show here that deuterium content does not necessarily inform on mechanism as IAD can catalyze the exchange of skatole's 3'-methyl hydrogens post- turnover. Structural comparisons show that both IAD and HPAD display structural features that are not found in other characterized GREs, suggesting that they represent a distinct GRE-subclass. Collectively, these insights will inform IAD inhibitor design aimed at decreasing skatole production.",
  "abstract_shown": true,
  "affiliations": [
    "Massachusetts Institute of Technology and Howard Hughes Medical Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "C. N. Imrich"
    },
    {
      "name": "L. R. F. Backman"
    },
    {
      "name": "A. P. Allworth"
    },
    {
      "name": "M. C. Andorfer"
    },
    {
      "name": "J. C. Paris"
    },
    {
      "name": "N. M. Greeley"
    },
    {
      "name": "B. Fu"
    },
    {
      "name": "E. P. Balskus"
    },
    {
      "affs": [
        0
      ],
      "name": "C. L. Drennan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2b0jnem4qkrza.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.05.24.727522",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.05.24.727522v3.full",
  "id": "2b0jnem4qkrza",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.05.24.727522v3",
  "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": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.05.24.727522v3.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2b0jnem4qkrza.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:49Z",
      "native_id": "10.64898/2026.05.24.727522",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.05.24.727522v3"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "The Structural Basis of Malodorant Skatole Formation by the Glycyl Radical Enzyme Indoleacetate Decarboxylase",
  "title_text": "The Structural Basis of Malodorant Skatole Formation by the Glycyl Radical Enzyme Indoleacetate Decarboxylase",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:49Z",
  "url": "https://research.draconitic.com/paper/2b0jnem4qkrza",
  "venue": "bioRxiv",
  "versions": [
    {
      "doi": "10.1073/pnas.2618341123",
      "pid": null,
      "relation": "published-as",
      "title": null,
      "venue": null
    }
  ]
}