{
  "abstract": "Water molecules are key actors in enzymatic proton-coupled electron transfer (PCET), yet their mechanistic versatility remains underexplored. Using a multiscale computational approach, we show that a previously unidentified water molecule (Wat3) in fatty acid photodecarboxylase (FAP), a natural photoenzyme converting fatty acids into alkanes, mediates radical quenching via two PCET pathways: in the dominant one, which qualitatively agrees with the 100 ns experimental time scale, Wat3 stabilizes the transition state for direct proton transfer from Cys432 to the alkyl radical; in the alternative, the same molecule acts as a proton shuttle in a quasi-concerted two-proton transfer, with the flavin semiquinone providing the electron in both cases. The minor pathway, though less accessible in wild-type FAP, may become operative in engineered variants or related enzymes. Additionally, CO2 reacts with the thiolate to yield a thiocarbonate adduct, explaining unassigned crystallographic electron density. These results show how a single water molecule encodes mechanistic diversity in enzymatic PCET.",
  "abstract_shown": true,
  "affiliations": [
    "University of L’aquila , , via Vetoio (Coppito 1) , ,",
    "Shanghai Jiao Tong University , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gianluca Dell’Orletta",
      "orcid": "0009-0009-4144-0903"
    },
    {
      "affs": [
        1
      ],
      "name": "Dongping Zhong",
      "orcid": "0000-0001-9381-8992"
    },
    {
      "affs": [
        0
      ],
      "name": "Massimiliano Aschi",
      "orcid": "0000-0003-2959-0158"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabella Daidone",
      "orcid": "0000-0001-8970-8408"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7ddbqg9y6qdmv.bib",
  "cited_by": 1,
  "doi": "10.1021/acsomega.6c06141",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737892/",
  "id": "7ddbqg9y6qdmv",
  "issns": [
    "2470-1343"
  ],
  "landing_url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c06141/5455830/A-Single-Active-Site-Water-Molecule-Encodes-Two",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1606|Photochemistry and Electron Transfer Studies"
    ]
  ],
  "openalex": "W7154103395",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acsomega.6c06141",
  "pmcid": "PMC13737892",
  "pmid": "42991562",
  "published": "2026-10-21",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/7ddbqg9y6qdmv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:39Z",
      "native_id": "10.1021/acsomega.6c06141",
      "source": "crossref",
      "url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c06141/5455830/A-Single-Active-Site-Water-Molecule-Encodes-Two"
    },
    {
      "first_seen": "2026-11-09T12:22:59Z",
      "native_id": "PMC13737892",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acsomega.6c06141"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1606|Photochemistry and Electron Transfer Studies",
      "subfield": "physical"
    }
  ],
  "title": "A Single Active-Site Water Molecule Encodes Two Distinct Proton-Coupled Electron Transfer Pathways in Fatty Acid Photodecarboxylase",
  "title_text": "A Single Active-Site Water Molecule Encodes Two Distinct Proton-Coupled Electron Transfer Pathways in Fatty Acid Photodecarboxylase",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:59Z",
  "url": "https://research.draconitic.com/paper/7ddbqg9y6qdmv",
  "venue": "ACS Omega",
  "versions": [
    {
      "doi": "10.26434/chemrxiv.15000883/v2",
      "pid": null,
      "relation": "preprint",
      "title": null,
      "venue": null
    },
    {
      "doi": "10.26434/chemrxiv.15000883/v3",
      "pid": null,
      "relation": "preprint",
      "title": null,
      "venue": null
    }
  ]
}