{
  "abstract": "Despite rapid advances in new-to-nature biocatalysis, trimolecular enzymatic reactions that generate previously inaccessible molecular entities, particularly those bearing well-defined, congested stereochemical dyads, remain exceedingly rare. Here, we report a novel diastereo- and enantioselective photobiocatalytic three-component radical coupling unknown in both organic chemistry and enzymology, enabled by cooperative catalysis employing an evolved pyridoxal biocatalyst and a transition-metal photosensitizer. Directed evolution using high-throughput photobiocatalysis furnished two threonine aldolase variants, enabling the stereoselective assembly of contiguous tri- and tetrasubstituted stereocenters as well as vicinal tetrasubstituted stereocenters, which were long regarded as a challenging goal for stereoselective radical chemistry and asymmetric catalysis. Furthermore, a variety of radical precursors, including alpha-iodoesters, alpha-iodoamides, alpha-iodoketones, and alpha-iodonitriles, could be transformed into structurally diverse, densely substituted non-canonical amino acid derivatives via C-H functionalization with excellent stereocontrol. Leveraging the broad substrate compatibility of engineered pyridoxal biocatalysts, combinatorial biocatalysis was achieved by simultaneously varying all three coupling partners, delivering products with a 98% success rate. Collectively, this diversity-generating multicomponent photobiocatalytic radical coupling afforded a powerful strategy for addressing long-standing challenges in asymmetric catalysis while enabling access to valuable stereochemically complex small molecules with applications in medicinal chemistry.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, Santa Barbara, California; Howard Hughes Medical Institute, University of California, Santa Barbara."
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Q. Hu"
    },
    {
      "name": "C.-X. Zheng"
    },
    {
      "name": "B. K. Mai"
    },
    {
      "name": "P. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5rfz9d3me2gpw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754468",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754468v1.full",
  "id": "5rfz9d3me2gpw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754468v1",
  "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",
      "1312|Enzyme Catalysis and Immobilization"
    ]
  ],
  "openalex": "W7214594867",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754468v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5rfz9d3me2gpw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:49Z",
      "native_id": "10.64898/2026.09.25.754468",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754468v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Enzyme Catalysis and Immobilization",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Asymmetric assembly of congested contiguous stereocenters via photobiocatalytic three-component radical coupling",
  "title_text": "Asymmetric assembly of congested contiguous stereocenters via photobiocatalytic three-component radical coupling",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:49Z",
  "url": "https://research.draconitic.com/paper/5rfz9d3me2gpw",
  "venue": "bioRxiv",
  "versions": []
}