Evidence map›Paper›PMID 25097262›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis.

Sarah Frusciante, Gianfranco Diretto, Mark Bruno, Paola Ferrante, Marco Pietrella, Alfonso Prado-Cabrero, Angela Rubio-Moraga, Peter Beyer, Lourdes Gomez-Gomez, Salim Al-Babili and 1 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
8.9field-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

124 citing papers in PubMed, 289 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Genome-Wide Analysis of TomatoPlants (Basel, Switzerland) · 2026
    Article
  6. Evolutionary adaptation of CCD4 enzymes inFrontiers in plant science · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
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  14. Temporal gene expression profiling suggests stage-specific regulation of apocarotenoid biosynthesis genes during stigma development inPhysiology and molecular biology of plants : an international journal of functional plant biology · 2025
    Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Potential therapeutic effects of crocin.Naunyn-Schmiedeberg's archives of pharmacology · 2024
    Review

64 more citing papers are in PubMed but not listed here.

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 at 4 institutions in 4 countries.

Sarah FruscianteItalian National Agency for New Technologies, Energy, and Sustainable Development, Casaccia Research Centre, 00123 Rome, Italy;Sapienza, University of Rome, 00185 Rome, Italy;
Gianfranco DirettoItalian National Agency for New Technologies, Energy, and Sustainable Development, Casaccia Research Centre, 00123 Rome, Italy;
Mark BrunoFaculty of Biology, University of Freiburg, D-79104 Freiburg, Germany;
Paola FerranteItalian National Agency for New Technologies, Energy, and Sustainable Development, Casaccia Research Centre, 00123 Rome, Italy;
Marco PietrellaItalian National Agency for New Technologies, Energy, and Sustainable Development, Casaccia Research Centre, 00123 Rome, Italy;
Alfonso Prado-CabreroCenter for Desert Agriculture, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia; and.
Angela Rubio-MoragaInstituto Botánico, Facultad de Farmacia, Universidad de Castilla-La Mancha, 02071 Albacete, Spain.
Peter BeyerFaculty of Biology, University of Freiburg, D-79104 Freiburg, Germany;
Lourdes Gomez-GomezInstituto Botánico, Facultad de Farmacia, Universidad de Castilla-La Mancha, 02071 Albacete, Spain.
Salim Al-BabiliFaculty of Biology, University of Freiburg, D-79104 Freiburg, Germany;Center for Desert Agriculture, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia; and.
Giovanni GiulianoItalian National Agency for New Technologies, Energy, and Sustainable Development, Casaccia Research Centre, 00123 Rome, Italy; giovanni.giuliano@enea.it.
King Abdullah University of Science and Technology · SAUniversity of Castilla-La Mancha · ESUniversity of Freiburg · DESapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Crocus sativus stigmas are the source of the saffron spice and accumulate the apocarotenoids crocetin, crocins, picrocrocin, and safranal, responsible for its color, taste, and aroma. Through deep transcriptome sequencing, we identified a novel dioxygenase, carotenoid cleavage dioxygenase 2 (CCD2), expressed early during stigma development and closely related to, but distinct from, the CCD1 dioxygenase family. CCD2 is the only identified member of a novel CCD clade, presents the structural features of a bona fide CCD, and is able to cleave zeaxanthin, the presumed precursor of saffron apocarotenoids, both in Escherichia coli and in maize endosperm. The cleavage products, identified through high-resolution mass spectrometry and comigration with authentic standards, are crocetin dialdehyde and crocetin, respectively. In vitro assays show that CCD2 cleaves sequentially the 7,8 and 7',8' double bonds adjacent to a 3-OH-β-ionone ring and that the conversion of zeaxanthin to crocetin dialdehyde proceeds via the C30 intermediate 3-OH-β-apo-8'-carotenal. In contrast, zeaxanthin cleavage dioxygenase (ZCD), an enzyme previously claimed to mediate crocetin formation, did not cleave zeaxanthin or 3-OH-β-apo-8'-carotenal in the test systems used. Sequence comparison and structure prediction suggest that ZCD is an N-truncated CCD4 form, lacking one blade of the β-propeller structure conserved in all CCDs. These results constitute strong evidence that CCD2 catalyzes the first dedicated step in crocin biosynthesis. Similar to CCD1, CCD2 has a cytoplasmic localization, suggesting that it may cleave carotenoids localized in the chromoplast outer envelope.

Indexed as

BiocatalysisCarotenoidsCrocusDioxygenasesMolecular Sequence DataSubstrate Specificitycarotenoid cleavage dioxygenase 1CarotenoidscrocinDioxygenasessymmetric carotenoid cleavageβ-citraurin

Identifiers

PMID25097262
PMCPMC4143034
OpenAlexW2058301861

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.