{
  "abstract": "Directed evolution and machine-learning-assisted evolution have transformed biocatalysis by enabling rapid optimisation of catalytic performance within compatible protein scaffolds. In parallel, advances in deep-learning-driven de novo protein design have expanded accessible protein architectural space, enabling the generation of functional catalysts for increasingly challenging transformations. We herein report a synergistic design-evolution strategy to encode new-to-nature regio- and enantioselective C-H amination reactions using engineered de novo haemproteins to synthesise chiral piperidines, a privileged pharmacophore in drug discovery. By integrating motif scaffolding, computational re-design, and directed evolution, we demonstrate de novo enzyme design can enable challenging, high-energy-barrier enzyme chemistry with programmable regio- and enantioselectivity, high catalytic efficiency, excellent enzyme stability, and scaffold diversity.",
  "abstract_shown": true,
  "affiliations": [
    "California Institute of Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Z.-Q. Li"
    },
    {
      "name": "R. K. Zhang"
    },
    {
      "name": "P.-P. Xie"
    },
    {
      "name": "J. Kelly"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "name": "Z.-Y. Qin"
    },
    {
      "name": "T. Lambert"
    },
    {
      "name": "O. Mukhopadhyay"
    },
    {
      "name": "D. Hanley"
    },
    {
      "name": "A. E. Danson"
    },
    {
      "name": "J. Abramson"
    },
    {
      "name": "S. Singh"
    },
    {
      "name": "Z. Wu"
    },
    {
      "name": "P. Kohli"
    },
    {
      "name": "P. Liu"
    },
    {
      "name": "J. Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "F. H. Arnold"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e3qbc214vhr2v.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.01.754751",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.754751v1.full",
  "id": "e3qbc214vhr2v",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.754751v1",
  "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",
      "synthetic biology"
    ],
    [
      "openalex",
      "1312|Enzyme Catalysis and Immobilization"
    ]
  ],
  "openalex": "W7216276710",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.754751v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e3qbc214vhr2v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:51Z",
      "native_id": "10.64898/2026.10.01.754751",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.01.754751v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:synthetic biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Design-Evolution Synergy Enables New-to-Nature Enzyme Chemistry",
  "title_text": "Design-Evolution Synergy Enables New-to-Nature Enzyme Chemistry",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:51Z",
  "url": "https://research.draconitic.com/paper/e3qbc214vhr2v",
  "venue": "bioRxiv",
  "versions": []
}