{
  "abstract": "Catalytic asymmetric dearomatization provides a powerful strategy for converting readily available aromatic feedstocks into valuable three-dimensional molecular scaffolds. Despite substantial advances over the past several decades, general methods for catalytic asymmetric dearomatization of electrophilic arenes, particularly non-heterocyclic substrates with high aromatic stabilization energies, remain a challenging task. Here, we report the use of a hydrogen atom transfer mechanism for biocatalytic radical dearomatization of electron-deficient arenes. Repurposing and directed evolution of our previously developed P450 halogen atom transferases furnished hydrogen atom transfer dearomatases that catalyze the stereoselective dearomatization of a range of electrophilic arenes, including electron-deficient indoles, pyrroles, and simple benzene derivatives. These evolved biocatalysts facilitated both diastereodivergent and enantiodivergent radical dearomatization, providing access to fused and spirocyclic chiral scaffolds bearing challenging quaternary and/or contiguous stereocenters. Computational and experimental studies revealed that a strategically positioned active-site lysine residue enables enzyme-controlled proton transfer against the intrinsic thermodynamic stereopreference, allowing catalyst-controlled reversal of diastereoselectivity from a common radical intermediate. Importantly, the evolved dearomatases efficiently transformed challenging arene substrates that proved recalcitrant under previously optimized Fe, Mn and Co-based metal-hydride hydrogen atom transfer conditions. Collectively, these results establish new-to-nature metalloredox biocatalysis as a powerful strategy for overcoming longstanding challenges in asymmetric radical catalysis.",
  "abstract_shown": true,
  "affiliations": [
    "University of California Santa Barbara"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "K. Lin"
    },
    {
      "name": "P.-P. Xie"
    },
    {
      "name": "Y. Tian"
    },
    {
      "name": "H. Chen"
    },
    {
      "name": "H. Chen"
    },
    {
      "name": "P. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3xpxrbe00dw4v.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.07.764688",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.07.764688v1.full",
  "id": "3xpxrbe00dw4v",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.07.764688v1",
  "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/10.64898/2026.11.07.764688v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3xpxrbe00dw4v.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:27:11Z",
      "native_id": "10.64898/2026.11.07.764688",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.07.764688v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "Biocatalytic Asymmetric Radical Dearomatization of Electrophilic Heterocyclic and Non-Heterocyclic Arenes",
  "title_text": "Biocatalytic Asymmetric Radical Dearomatization of Electrophilic Heterocyclic and Non-Heterocyclic Arenes",
  "type": "preprint",
  "updated_at": "2026-11-10T00:27:11Z",
  "url": "https://research.draconitic.com/paper/3xpxrbe00dw4v",
  "venue": "bioRxiv",
  "versions": []
}