Evidence map›Paper›PMID 37932529›Full record

ArticleNature chemical biology2023

Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast.

Samuel A Bradley, Beata J Lehka, Frederik G Hansson, Khem B Adhikari, Daniela Rago, Paulina Rubaszka, Ahmad K Haidar, Ling Chen, Lea G Hansen, Olga Gudich and 22 more

Open access · hybridAbstract read
In one paragraph

Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
13.1field-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

26 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
  2. Cinchona alkaloid scaffold decoded.Plant communications · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Engineering chronological lifespan toward a robust yeast cell factory.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Peptidic Tryptophan Halogenation by a Promiscuous Flavin-Dependent Enzyme.Angewandte Chemie (International ed. in English) · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. 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

32 authors at 6 institutions in 5 countries.

Samuel A Bradley *Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Beata J Lehka *Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Frederik G HanssonNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Khem B AdhikariNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Daniela RagoNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Paulina RubaszkaNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Ahmad K HaidarNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Ling ChenNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Lea G HansenNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0002-8454-312X
Olga GudichNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Konstantina GiannakouNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Bettina LenggerNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0001-9997-7011
Ryan T GillNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Yoko NakamuraDepartment of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.
Thomas Dugé de BernonvilleEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.ORCID 0000-0002-2205-2886
Konstantinos KoudounasEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.ORCID 0000-0002-6000-6565
David Romero-SuarezNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0003-3491-3521
Ling DingDepartment of Bioengineering, Technical University of Denmark, Lyngby, Denmark.
Yijun QiaoDepartment of Bioengineering, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0001-7473-0442
Thomas M FrimurerNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-9682-8245
Anja A PetersenNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Sébastien BesseauEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.ORCID 0000-0002-5518-2580
Sandeep KumarEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.
Nicolas GautronEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.ORCID 0000-0002-2184-7302
Celine MelinEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.
Jillian MarcEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.
Remi JeanneauAxyntis, Pithiviers, France.
Sarah E O'ConnorDepartment of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, Germany.ORCID 0000-0003-0356-6213
Vincent CourdavaultEA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, Tours, France.ORCID 0000-0001-8902-4532
Jay D KeaslingNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Jie ZhangNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark. jzha@biosustain.dtu.dk.ORCID 0000-0003-4119-9442
Michael K JensenNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark. mije@biosustain.dtu.dk.ORCID 0000-0001-7574-4707
Novo Nordisk Foundation · DKUniversité de Tours · FRMax Planck Institute for Chemical Ecology · DETechnical University of Denmark · DKUniversity of Copenhagen · DKLawrence Berkeley National Laboratory · US

Funding

Danmarks Grundforskningsfond (Danish National Research Foundation) DNRF137EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 814645Novo Nordisk Fonden (Novo Nordisk Foundation) NNF19SA0035438Novo Nordisk Fonden (Novo Nordisk Foundation) NNF20CC0035580
6 · The paper itself

Abstract

Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker's yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.

Indexed as

CatharanthusSaccharomyces cerevisiaeIndole AlkaloidsMonoterpenesPharmaceutical PreparationsPlant ProteinsPlantsIndole AlkaloidsMonoterpenesPharmaceutical PreparationsPlant Proteins

Identifiers

PMID37932529
PMCPMC10667104
OpenAlexW4388425262

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.