Evidence map›Paper›PMID 36050299›Full record

ArticleNature communications2022

A gene cluster in Ginkgo biloba encodes unique multifunctional cytochrome P450s that initiate ginkgolide biosynthesis.

Victor Forman, Dan Luo, Fernando Geu-Flores, René Lemcke, David R Nelson, Sotirios C Kampranis, Dan Staerk, Birger Lindberg Møller, Irini Pateraki

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
20.7field-weighted citation impact, top 1% of its field
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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Construction of a globally modular recombinantSynthetic and systems biotechnology · 2026
    Article
  3. Article
  4. Review
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  7. Enhancement of levopimaradiene production inChinese herbal medicines · 2026
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Identification of a central regulator of ginkgolide biosynthesis inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Plant sesquiterpene lactones.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  17. Article
  18. Article
  19. Review
  20. Review
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

9 authors at 2 institutions in 2 countries.

Victor FormanFaculty of Science, Department of Plant and Environmental Sciences, Section for Plant Biochemistry, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-4943-6721
Dan LuoFaculty of Science, Department of Plant and Environmental Sciences, Section for Plant Biochemistry, University of Copenhagen, Copenhagen, Denmark.
Fernando Geu-FloresFaculty of Science, Department of Plant and Environmental Sciences, Section for Plant Biochemistry, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-5735-9810
René LemckeFaculty of Health and Medical Sciences, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-4903-4741
David R NelsonFaculty of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, University of Tennessee, Memphis, TN, USA.
Sotirios C KampranisFaculty of Science, Department of Plant and Environmental Sciences, Section for Plant Biochemistry, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-6208-1684
Dan StaerkFaculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-0074-298X
Birger Lindberg MøllerFaculty of Science, Department of Plant and Environmental Sciences, Section for Plant Biochemistry, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-3252-3119
Irini PaterakiFaculty of Science, Department of Plant and Environmental Sciences, Section for Plant Biochemistry, University of Copenhagen, Copenhagen, Denmark. eipa@plen.ku.dk.ORCID 0000-0002-7526-2334
University of Copenhagen · DKUniversity of Tennessee Health Science Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ginkgo tree (Ginkgo biloba) is considered a living fossil due to its 200 million year's history under morphological stasis. Its resilience is partly attributed to its unique set of specialized metabolites, in particular, ginkgolides and bilobalide, which are chemically complex terpene trilactones. Here, we use a gene cluster-guided mining approach in combination with co-expression analysis to reveal the primary steps in ginkgolide biosynthesis. We show that five multifunctional cytochrome P450s with atypical catalytic activities generate the tert-butyl group and one of the lactone rings, characteristic of all G. biloba trilactone terpenoids. The reactions include scarless C-C bond cleavage as well as carbon skeleton rearrangement (NIH shift) occurring on a previously unsuspected intermediate. The cytochrome P450s belong to CYP families that diversifies in pre-seed plants and gymnosperms, but are not preserved in angiosperms. Our work uncovers the early ginkgolide pathway and offers a glance into the biosynthesis of terpenoids of the Mesozoic Era.

Indexed as

Cytochrome P-450 Enzyme SystemGinkgo bilobaGinkgolidesHumansLactonesMultigene FamilyPlant ExtractsTerpenesCytochrome P-450 Enzyme SystemGinkgolidesLactonesPlant ExtractsTerpenes

Identifiers

PMID36050299
PMCPMC9436924
OpenAlexW4294052668

What OpenQuestion holds

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Registered trials

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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.