{
  "abstract": "Catalyst-controlled stereodivergent synthesis of acyclic molecules bearing multiple stereogenic centers remains a longstanding challenge in asymmetric catalysis, particularly through intermolecular radical C-C coupling. Here, we report the directed evolution of pyridoxal 5'-phosphate (PLP)-dependent biocatalysts for the stereodivergent synthesis of non canonical amino acids bearing either skipped , {gamma}-stereochemical dyads or contiguous , {beta}, {gamma}-stereochemical triads. Starting from a thermophilic tryptophan synthase {beta}-subunit, protein engineering generated complementary enzyme variants that selectively construct three of the four possible , {gamma}-stereoisomers through biocatalyst-controlled reversal of both remote {gamma}-stereochemistry and proximal -stereochemistry. These engineered enzymes catalyzed intermolecular radical C-C bond formation with a broad range of secondary alkyltrifluoroborates, affording , {gamma}-disubstituted amino acids in excellent yields and stereoselectivities. Furthermore, directed evolution enabled efficient {beta}-dehydroxylative radical coupling of the non-native threonine-derived aminoacrylate intermediate, providing amino acids bearing contiguous , {beta}, {gamma}-stereochemical triads with up to 96:4:<0.1:<0.1 d.r. and >99:1 e.r.. To further demonstrate the synthetic utility of this platform, the stereochemically enriched amino acids were transformed into valuable {gamma}-chiral amines through engineered PLP dependent tryptophan decarboxylases, establishing a dual PLP enzyme based biocatalytic cascade for the enantiodivergent synthesis of privileged amine scaffolds. Molecular dynamics simulations reveal that enzyme controlled {gamma}-stereoselectivity originates from active-site remodeling that modulates {pi}-{pi} interactions and steric contacts governing the facial selectivity of the radical addition step. This work expands the synthetic capabilities of radical biocatalysis by enabling catalyst-controlled stereodivergent assembly of complex acyclic stereochemical arrays and establishes engineered PLP enzymes as versatile catalysts for the synthesis of stereochemically complex amino acids and chiral amines.",
  "abstract_shown": true,
  "affiliations": [
    "University of California Santa Barbara"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Z. Bo"
    },
    {
      "name": "L. Cheng"
    },
    {
      "name": "X. Zhang"
    },
    {
      "name": "A. Singh"
    },
    {
      "name": "P. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dhpfgr4af4mp6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.757362",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757362v1.full",
  "id": "dhpfgr4af4mp6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757362v1",
  "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": "W7221121651",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757362v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dhpfgr4af4mp6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:46Z",
      "native_id": "10.64898/2026.10.07.757362",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757362v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Enzyme Catalysis and Immobilization",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Photobiocatalytic Diastereo- and Enantioselective Synthesis of Non-Canonical Amino Acids Bearing Challenging Stereochemical Dyads and Triads",
  "title_text": "Photobiocatalytic Diastereo- and Enantioselective Synthesis of Non-Canonical Amino Acids Bearing Challenging Stereochemical Dyads and Triads",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:46Z",
  "url": "https://research.draconitic.com/paper/dhpfgr4af4mp6",
  "venue": "bioRxiv",
  "versions": []
}