{
  "abstract": "Nucleoside analogues such as vidarabine (Ara-A) are vital therapeutics but are often limited by poor pharmacokinetics. Its phosphorylated form, vidarabine 5′-monophosphate (Ara-AMP), offers improved solubility and is used as a clinical alternative, although it can be dephosphorylated to Ara-A in vivo. Here, we report a modular multienzyme cascade for the sustainable synthesis of Ara-AMP directly from adenosine. The cascade integrates three functional modules: a core module (PNP, PPM, and RpiA) for the conversion of adenosine to Ara-A, a driver module (dNKδ20) for the selective phosphorylation of Ara-A to Ara-AMP, and a support module (PPK) for ATP regeneration from low-cost ADP and polyphosphate. The use of dNKδ20, a mutant deoxyribonucleoside kinase with high selectivity for Ara-A over adenosine, is critical for minimizing the formation of AMP byproduct, which would otherwise complicate downstream processing. Under optimized conditions, the cascade achieved an 80.2% conversion of 1 mM adenosine to Ara-AMP in 4 h using 0.05 mM ADP. The modular design was also applicable to guanosine and inosine, affording the corresponding arabinosyl nucleotides, albeit with lower yields. This work establishes a sustainable biocatalytic platform for nucleoside analogues, exemplifying how enzyme promiscuity, thermodynamic driving, and cofactor recycling enable green pharmaceutical manufacturing.",
  "abstract_shown": true,
  "affiliations": [
    "Henan Engineering Center of Bioconversion Technology of Functional Microbes, College of Life Science, Henan Normal University, Xinxiang, 453007, People's Republic of China",
    "MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, Dalian, 116024, People's Republic of China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Weiwei Su"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaofan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Rongrong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaige Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaojia Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaobei Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhenyu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hailei Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuxue Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8df90zcf4sqhy.bib",
  "cited_by": 0,
  "doi": "10.1016/j.synbio.2026.10.005",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696763/",
  "id": "8df90zcf4sqhy",
  "issns": [
    "2405-805X"
  ],
  "landing_url": "https://doi.org/10.1016/j.synbio.2026.10.005",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research Article"
    ],
    [
      "openalex",
      "1312|Enzyme Catalysis and Immobilization"
    ]
  ],
  "openalex": "W7222483839",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696763/pdf/?tool=EBI",
  "pmcid": "PMC13696763",
  "pmid": "42936124",
  "published": "2026-10-16",
  "publisher": "KeAi Publishing",
  "ris": "https://research.draconitic.com/paper/8df90zcf4sqhy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:03Z",
      "native_id": "PMC13696763",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.synbio.2026.10.005"
    },
    {
      "first_seen": "2026-10-30T12:21:25Z",
      "native_id": "PMC:PMC13696763",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13696763"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Enzyme Catalysis and Immobilization",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A modular in vitro multienzyme cascade for the sustainable synthesis of high-value vidarabine 5′-monophosphate from adenosine",
  "title_text": "A modular in vitro multienzyme cascade for the sustainable synthesis of high-value vidarabine 5′-monophosphate from adenosine",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:02Z",
  "url": "https://research.draconitic.com/paper/8df90zcf4sqhy",
  "venue": "Synthetic and Systems Biotechnology",
  "versions": []
}