{
  "abstract": "Enzymes are unparalleled catalysts that combine high activity and selectivity with operation under mild conditions. Despite these advantages, their broader use as industrial biocatalysts is limited by insufficient stability under process-relevant conditions and by the difficulty of achieving site-specific chemical functionalization. Simultaneously enhancing protein stability and enabling site-specific functionalization through a single chemical strategy remains a central challenge, particularly, when addressing multimeric enzymes. Here, we show that a four-armed crosslinker with tetrahedral symmetry enables simultaneous stabilization and programmable functionalization of the tetrameric enzyme borneol dehydrogenase. A twostep crosslinking–modification reaction yields a well-defined and stable protein quaternary architecture with an incorporated reactive handle, enabling the installation of diverse functionalities, including bioorthogonal tags and functional groups for immobilization. The chemically engineered bicyclic enzyme exhibits remarkably enhanced thermal stability and resistance to organic cosolvents, which results in exceptional longevity supporting ten weeks of continuous flow operation. Unlike previous methods that decouple stabilization from modification, this strategy unites structural reinforcement and functionalization, thereby expanding the scope of chemical protein engineering.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry and Pharmaceutical Sciences, VU University Amsterdam, De Boelelaan 1108, Amsterdam, Netherlands, 1081 HZ",
    "Incircular B.V., De Boelelaan 1108, Amsterdam, Netherlands, 1081 HZ",
    "Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstr. 2, Göttingen, Germany, 37077"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Juan Lizandra Pérez"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "George H. Hutchins"
    },
    {
      "affs": [
        0
      ],
      "name": "Rasmus Klintrot"
    },
    {
      "affs": [
        0
      ],
      "name": "Pascal Poc"
    },
    {
      "affs": [
        0
      ],
      "name": "Leonardo Romão Soares"
    },
    {
      "affs": [
        0
      ],
      "name": "Ivana Drienovska"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Sven Hennig"
    },
    {
      "affs": [
        1
      ],
      "name": "Saskia Neubacher"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Tom N. Grossmann",
      "orcid": "0000-0003-0179-4116"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dcyzksm6hwfax.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008156/v1",
  "fulltext_url": null,
  "id": "dcyzksm6hwfax",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008156/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Enzyme Catalysis and Immobilization"
    ]
  ],
  "openalex": "W7204902528",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008156/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/dcyzksm6hwfax.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008156",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008156/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Enzyme Catalysis and Immobilization",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Stabilization and Functionalization of an Enzyme Complex via Modular In Situ Conjugation",
  "title_text": "Stabilization and Functionalization of an Enzyme Complex via Modular In Situ Conjugation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/dcyzksm6hwfax",
  "venue": "ChemRxiv",
  "versions": []
}