Evidence map›Paper›PMID 41290611›Full record

ArticleNature communications2025

Ancient gene clusters govern the initiation of monoterpenoid indole alkaloid biosynthesis and C3 stereochemistry inversion.

Jaewook Hwang, Jonathan Kirshner, Daniel André Ramey Deschênes, Matthew Bailey Richardson, Steven J Fleck, Scott Galeung Alexander Mann, Jun Guo, Jacob Owen Perley, Mohammadamin Shahsavarani, Jorge Jonathan Oswaldo Garza-Garcia and 12 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Tuning reductase activity in monoterpene indole alkaloid biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Discovery of a Plant Pictet-Spenglerase With R-Stereoselectivity.Angewandte Chemie (International ed. in English) · 2026
    Article
  4. Article
  5. Article
  6. 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

22 authors.

Jaewook Hwang *Department of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Jonathan Kirshner *Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.ORCID http://orcid.org/0009-0008-5521-0351
Daniel André Ramey DeschênesDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Matthew Bailey RichardsonDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Steven J FleckDepartment of Biological Sciences, University at Buffalo, Buffalo, NY, USA.ORCID http://orcid.org/0000-0001-5370-2258
Scott Galeung Alexander MannDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Jun GuoDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.ORCID http://orcid.org/0000-0002-4681-6983
Jacob Owen PerleyDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Mohammadamin ShahsavaraniDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Jorge Jonathan Oswaldo Garza-GarciaDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Alyssa Dawn SeveckDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Savannah Sadie DoironDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Zhan MaiDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Stephen Nelson SilliphantDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Sarah Anne EnglehartDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Barry A BlightDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Larry CalhounDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada.
Di GaoKey Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China.
Jiazhang LianKey Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0001-9784-9876
Ghislain DeslongchampsDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada. ghislain@unb.ca.ORCID http://orcid.org/0000-0002-3184-3807
Victor A AlbertDepartment of Biological Sciences, University at Buffalo, Buffalo, NY, USA. vaalbert@buffalo.edu.ORCID http://orcid.org/0000-0002-0262-826X
Yang QuDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada. yang.qu@unb.ca.ORCID http://orcid.org/0000-0002-0847-7212

Funding

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) RGPIN-2020-04133National Science Foundation (NSF) 2030871New Brunswick Innovation Foundation (Fondation de l'innovation du Nouveau-Brunswick) RAI_2023_054, RPI_2022_002
6 · The paper itself

Abstract

The inversion of C3 stereochemistry in monoterpenoid indole alkaloids (MIAs), derived from the central precursor strictosidine (3S), is essential for producing pharmacologically important 3 R MIAs and spirooxindoles such as reserpine. While early MIA biosynthesis preserves the 3S configuration, the mechanism underlying C3 inversion has remained unresolved. Here, we identify and biochemically characterize a conserved oxidase-reductase pair in Gentianales: heteroyohimbine/yohimbine/corynanthe C3-oxidase (HYC3O) and C3-reductase (HYC3R), which together invert the 3S stereochemistry to 3 R across diverse substrates. HYC3O and HYC3R are encoded within biosynthetic gene clusters in Rauvolfia tetraphylla and Catharanthus roseus, homologous to a geissoschizine synthase (GS) cluster also uncovered. Comparative genomics indicate that the GS cluster originated at the base of Gentianales (~135 Mya), coinciding with the evolution of the strictosidine synthase cluster, whereas the reserpine cluster arose later. These findings uncover the genomic and biochemical basis of key events driving MIA diversification beyond canonical vinblastine and ajmaline pathways.

Indexed as

Multigene FamilySecologanin Tryptamine AlkaloidsBiosynthetic PathwaysCatharanthusEvolution, MolecularOxidoreductasesPhylogenyPlant ProteinsRauwolfiaStereoisomerismVinca AlkaloidsOxidoreductasesPlant ProteinsSecologanin Tryptamine AlkaloidsstrictosidineVinca Alkaloids

Identifiers

PMID41290611
PMCPMC12647599

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.