{
  "abstract": "Enzymatic nitrene-induced dearomatization represents an unexplored area of biocatalytic reactivity. Here, we report the directed evolution of AsqJ, a non-heme iron enzyme from aspoquinolone biosynthesis, to catalyze the first biocatalytic asymmetric dearomative nitrene transfer into indoles to furnish enantioenriched 3a-aminopyrroloindolines — a privileged scaffold in bioactive indole alkaloid natural products. Obtained through iterative semi-rational engineering and structure-informed mutagenesis, the final variant achieves up to 98% yield and >99% ee. The reaction accommodates a range of indole substrates, affording up to 86% isolated yield on preparative scale with consistently high enantioselectivity. Molecular dynamics simulations suggest that directed evolution established a new substrate-binding conformation that is distinct from the starting variant through a reorganized hydrogen-bonding network within a more preorganized active site. The synthetic utility of this platform is demonstrated through the total syntheses of two natural products, (+)-psychotriasine and (+)-psychotrimine. This work establishes asymmetric dearomative nitrene transfer as a new biocatalytic modality, extends the catalytic repertoire of non-heme iron enzymes to encompass asymmetric dearomatization, and provides a foundation for applying new-to-nature biocatalytic reactions in complex natural product synthesis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, BioScience Research Collaborative",
    "Rice University",
    "Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences",
    "Polytechnic University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinpeng Mu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ruiying Jiang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jiali Xie"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Shu Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hans Renata",
      "orcid": "0000-0003-2468-2328"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/11t67akk8scpw.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008359/v1",
  "fulltext_url": null,
  "id": "11t67akk8scpw",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008359/v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Enzyme Catalysis and Immobilization"
    ]
  ],
  "openalex": "W7211916582",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-06",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/11t67akk8scpw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008359",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008359/v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Enzyme Catalysis and Immobilization",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Directed Evolution of a Non-Heme Iron Enzyme for Enantioselective Dearomative Nitrene Transfer: Synthesis of 3a-Aminopyrroloindoline Alkaloids",
  "title_text": "Directed Evolution of a Non-Heme Iron Enzyme for Enantioselective Dearomative Nitrene Transfer: Synthesis of 3a-Aminopyrroloindoline Alkaloids",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/11t67akk8scpw",
  "venue": "ChemRxiv",
  "versions": []
}