{
  "abstract": "Nicotine is a neuroactive alkaloid produced by tobacco (Nicotiana tabacum) as a defence against herbivory, and an addictive stimulant that has been used by humans for millennia. Despite its significance, the core steps of its biosynthesis have remained elusive. Here, we demonstrate the in vitro reconstruction of a four-enzyme stereoselective biocatalytic cascade that forms (S)-nicotine from nicotinic acid and N-methylpyrrolinium. This cascade includes two glucose-processing enzymes that participate in a cryptic activating glucosylation step. We also reconstruct this pathway in planta and present high resolution X-ray structures of the key carbon-carbon bond forming reductase-oxidase pair bound to their substrate and product, respectively. This work establishes the complete biosynthetic pathway to nicotine, providing new gene targets for controlling alkaloid production in Nicotiana and unlocking enzymatic routes to pyridine alkaloids.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Novel Agricultural Products, Department of Biology, University of York, York, UK",
    "Department of Chemistry, University of York, York, UK",
    "Section for Plant Biochemistry and Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark",
    "York Biomedical Research Institute, University of York, York, UK",
    "Centre for Novel Agricultural Products, Department of Biology, University of York, York, UK. benjamin.lichman@york.ac.uk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Benjamin T. W. Schwabe",
      "orcid": "0009-0009-4850-9838"
    },
    {
      "affs": [
        2
      ],
      "name": "Isabelle Angstman"
    },
    {
      "affs": [
        2
      ],
      "name": "Katharina Vollheyde",
      "orcid": "0000-0002-9592-4470"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zoe Ingold",
      "orcid": "0000-0003-1456-5080"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiacheng Li",
      "orcid": "0000-0002-4404-4895"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Ksenia S. Stankevich",
      "orcid": "0000-0002-6701-7582"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Christopher D. Spicer",
      "orcid": "0000-0001-8787-578X"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Martin A. Fascione",
      "orcid": "0000-0002-0066-4419"
    },
    {
      "affs": [
        1
      ],
      "name": "Gideon Grogan",
      "orcid": "0000-0003-1383-7056"
    },
    {
      "affs": [
        2
      ],
      "name": "Fernando Geu‐Flores",
      "orcid": "0000-0002-5735-9810"
    },
    {
      "affs": [
        4
      ],
      "name": "Benjamin R. Lichman",
      "orcid": "0000-0002-0033-1120"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4kbkyx4v9hxdx.bib",
  "cited_by": 12,
  "doi": "10.1038/s41467-026-72705-0",
  "fulltext_url": null,
  "id": "4kbkyx4v9hxdx",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-72705-0",
  "language": "en",
  "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",
      "1312|Plant biochemistry and biosynthesis"
    ]
  ],
  "openalex": "W7161541149",
  "pdf_url": "https://www.nature.com/articles/s41467-026-72705-0.pdf",
  "pmcid": "PMC13184244",
  "pmid": "42151135",
  "published": "2026-05-18",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/4kbkyx4v9hxdx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7161541149",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-72705-0"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Plant biochemistry and biosynthesis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Nicotine biosynthesis is completed by cryptic activating glucosylation",
  "title_text": "Nicotine biosynthesis is completed by cryptic activating glucosylation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:07Z",
  "url": "https://research.draconitic.com/paper/4kbkyx4v9hxdx",
  "venue": "Nature Communications",
  "versions": []
}