Evidence map›Paper›PMID 42151135›Full record

ArticleNature communications2026

Nicotine biosynthesis is completed by cryptic activating glucosylation.

Benjamin T W Schwabe, Isabelle M Angstman, Katharina Vollheyde, Zoe Ingold, Jiacheng Li, Ksenia S Stankevich, Christopher D Spicer, Martin A Fascione, Gideon Grogan, Fernando Geu-Flores and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. How tobacco builds nicotine.Nature chemical biology · 2026
    Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Benjamin T W SchwabeCentre for Novel Agricultural Products, Department of Biology, University of York, York, UK.ORCID http://orcid.org/0009-0009-4850-9838
Isabelle M AngstmanSection for Plant Biochemistry and Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark.
Katharina VollheydeSection for Plant Biochemistry and Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark.ORCID http://orcid.org/0000-0002-9592-4470
Zoe IngoldCentre for Novel Agricultural Products, Department of Biology, University of York, York, UK.ORCID http://orcid.org/0000-0003-1456-5080
Jiacheng LiDepartment of Chemistry, University of York, York, UK.
Ksenia S StankevichDepartment of Chemistry, University of York, York, UK.ORCID http://orcid.org/0000-0002-6701-7582
Christopher D SpicerDepartment of Chemistry, University of York, York, UK.ORCID http://orcid.org/0000-0001-8787-578X
Martin A FascioneDepartment of Chemistry, University of York, York, UK.ORCID http://orcid.org/0000-0002-0066-4419
Gideon GroganDepartment of Chemistry, University of York, York, UK.ORCID http://orcid.org/0000-0003-1383-7056
Fernando Geu-FloresSection for Plant Biochemistry and Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark.ORCID http://orcid.org/0000-0002-5735-9810
Benjamin R LichmanCentre for Novel Agricultural Products, Department of Biology, University of York, York, UK. benjamin.lichman@york.ac.uk.ORCID http://orcid.org/0000-0002-0033-1120

Funding

Det Frie Forskningsråd (Danish Council for Independent Research) 5281-00267BRCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/T007222/1Research Councils UK (RCUK) MR/S01862X/1Research Councils UK (RCUK) MR/X010260/1
6 · The paper itself

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.

Indexed as

NicotianaNicotineAlkaloidsCrystallography, X-RayGlucoseGlycosylationPlant ProteinsAlkaloidsGlucoseNicotinePlant Proteins

Identifiers

PMID42151135
PMCPMC13184244

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.