{
  "abstract": "Biocatalysis continues to advance sustainable synthesis while relying on analytical technologies that can match the demands of high-throughput, miniaturized screening and complex assay formats. In particular, multiplexed substrate screening strategy accelerates enzyme discovery and the expansion of the enzyme toolbox, yet it demands greater selectivity, sensitivity, and throughput than conventional single-quadrupole LC-MS can provide. Here, an integrated high-throughput mass spectrometry framework enabling both quantitative targeted analysis and untargeted product discovery in biocatalytic reactions is introduced. The platform employs a tiered measurement strategy consisting of Acoustic Droplet Ejection-Multiple Reaction Monitoring Mass Spectrometry (ADE-MRM-MS) for targeted quantitation, Acoustic Droplet Ejection-Time-of-Flight Mass Spectrometry (ADE-TOF-MS) for untargeted product discovery through extracted ion chromatogram (XIC) analysis, and Acoustic Droplet Ejection-Quadrupole Time-of-Flight Tandem Mass Spectrometry (ADE-QTOF-MS/MS) for challenging selectivity scenarios involving near-isobaric compounds, closely related masses, and structural isomers. Application of this approach streamlined rapid discovery and evolution campaigns across pyrimidine nucleoside phosphorylases (PyNPs), transaminases (TAs), and nucleoside deoxyribosyltransferases (NDTs). Together, these results established the first unified ADE-MS framework for biocatalysis that delivers the speed, selectivity, and scalability required for next-generation biocatalyst screening and sustainable synthesis.",
  "abstract_shown": true,
  "affiliations": [
    "Pharmaceutical Analysis & Digital Technologies",
    "Merck & Co., Inc.",
    "Process Research & Development"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Wenxuan Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Devin Makey"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Vladimir Shchurik"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Giulio Fittolani"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Jennifer L. Kennemur"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Richard S. Ayikpoe"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Wai-Ling Cheung-Lee"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Chunyu Wu"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "John A. McIntosh"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Karla M. Camacho Soto"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rodell C. Barrientos"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Erik L. Regalado"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Emmanuel Appiah-Amponsah"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sasidhar N. Nirudodhi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6jdj5pgqth2jb.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010437/v1",
  "fulltext_url": null,
  "id": "6jdj5pgqth2jb",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010437/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1607|Mass Spectrometry Techniques and Applications"
    ]
  ],
  "openalex": "W7221756692",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010437/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/6jdj5pgqth2jb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010437",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010437/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Mass Spectrometry Techniques and Applications",
      "subfield": "physical"
    }
  ],
  "title": "Integrated High-Throughput Mass Spectrometry Framework for Multiplexed Substrate Screening in Enzyme Discovery and Development",
  "title_text": "Integrated High-Throughput Mass Spectrometry Framework for Multiplexed Substrate Screening in Enzyme Discovery and Development",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/6jdj5pgqth2jb",
  "venue": "ChemRxiv",
  "versions": []
}