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, Alyssa Dawn Seveck, Savannah Sadie Doiron, Zhan Mai, Stephen Nelson Silliphant, Sarah Anne Englehart, Barry A. Blight, Larry Calhoun, Di Gao, Jiazhang Lian, Ghislain Deslongchamps (), Victor A. Albert () and Yang Qu ()
Additional contact information
Jaewook Hwang: University of New Brunswick, Department of Chemistry
Jonathan Kirshner: University at Buffalo, Department of Biological Sciences
Daniel André Ramey Deschênes: University of New Brunswick, Department of Chemistry
Matthew Bailey Richardson: University of New Brunswick, Department of Chemistry
Steven J. Fleck: University at Buffalo, Department of Biological Sciences
Scott Galeung Alexander Mann: University of New Brunswick, Department of Chemistry
Jun Guo: University of New Brunswick, Department of Chemistry
Jacob Owen Perley: University of New Brunswick, Department of Chemistry
Mohammadamin Shahsavarani: University of New Brunswick, Department of Chemistry
Jorge Jonathan Oswaldo Garza-Garcia: University of New Brunswick, Department of Chemistry
Alyssa Dawn Seveck: University of New Brunswick, Department of Chemistry
Savannah Sadie Doiron: University of New Brunswick, Department of Chemistry
Zhan Mai: University of New Brunswick, Department of Chemistry
Stephen Nelson Silliphant: University of New Brunswick, Department of Chemistry
Sarah Anne Englehart: University of New Brunswick, Department of Chemistry
Barry A. Blight: University of New Brunswick, Department of Chemistry
Larry Calhoun: University of New Brunswick, Department of Chemistry
Di Gao: Zhejiang University, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering
Jiazhang Lian: Zhejiang University, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering
Ghislain Deslongchamps: University of New Brunswick, Department of Chemistry
Victor A. Albert: University at Buffalo, Department of Biological Sciences
Yang Qu: University of New Brunswick, Department of Chemistry

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65543-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65543-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65543-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().