Genome-wide survey uncovers 16 key terpene gene clusters in Euphorbiaceae
image: Collinearity analysis of casbene gene clusters in Euphorbiaceae species. The ancestral collinearity. relationships within casbene gene clusters are indicated by bold connections, while other syntenic gene relationships are shown with secondary connections. The analysis reveals stronger retention of genes within casbene clusters across multiple Euphorbiaceae species, including R. communis, E. peplus, V. fordii, V. montana, H. brasiliensis, and J. curcas.. Image link: https://academic.oup.com/hr/article/12/7/uhaf097/8145532#521871611
Credit: Horticulture Research
Euphorbiaceae is a large plant family containing ornamental and medicinal species, well known for producing bicyclic diterpenes with anti-tumor and antiviral activities. More than 650 macrocyclic diterpenoids have been reported across the group, yet the gene clusters responsible for synthesizing these compounds are poorly characterized. Although algorithms for biosynthetic cluster mining exist, their performance in complex plant genomes remains limited. A systematic approach to discover terpene gene clusters would accelerate research on pathway evolution, high-value metabolite production, and breeding of stress-tolerant varieties. Due to these challenges, there is a need to conduct in-depth research on terpene biosynthetic gene clusters in Euphorbiaceae.
Researchers from the Chinese Academy of Forestry reported (DOI: 10.1093/hr/uhaf097) the first genome-wide terpene gene cluster prediction pipeline for Euphorbiaceae on May 23 2025 in Horticulture Research. Integrating genomic, transcriptomic, and metabolic pathway data, the team identified 1824 putative clusters and refined them to 16 high-confidence terpene clusters. The work highlights casbene and casbene-derived diterpenoid clusters and offers critical resources for understanding terpene biosynthesis, evolution, and application potential across the family.
Using E2P2 enzyme prediction, Pathway Tools metabolic mapping, and PlantClusterFinder screening, researchers analyzed seven Euphorbiaceae genomes. Among 1824 initial clusters, 16 met stringent criteria involving TPS/CYP association, copathway involvement, and coexpression support.
A key finding is the casbene gene cluster on Chromosome 4 of Ricinus communis, containing 13 genes including LOC8259981 and LOC8259984 (casbene synthase genes), six CYP450 proteins (CYP80C9, CYP726A18, CYP726A16, CYP726A15, CYP726A14, CYP726A13), two ADH proteins, one BAHD acyltransferase, and additional monoterpene and sesquiterpene synthase proteins. Expression analysis showed leaf and seed-dominant coexpression patterns, revealing coordinated diterpene synthesis.
In Euphorbia peplus, casbene-derived pathways were identified, with CYP726A4 and CYP71D365 highly expressed in stems, while CYP726A626 was latex-enriched. Evolution analysis suggests loss or divergence of the cluster in Manihot esculenta, whereas Vernicia montana retained a root-specific casbene cluster lacking the neocembrene synthase gene, indicating metabolic specialization.
These results define biosynthetic modules linked to pharmacologically active diterpenoids and provide a scalable framework for cluster discovery in non-model species.
Dr. Yinhang Wang states that integrating prediction with pathway validation and coexpression filtering greatly improves terpene gene cluster resolution. The team notes that discovering casbene-related modules clarifies biosynthetic logic for diterpenoids such as ingenanes and jatrophanes and offers targets for future metabolic engineering. “Our pipeline bridges omics data and functional gene discovery,” Wang explains, “and will support synthetic biology, drug molecule exploration, and the mining of new terpene structures in Euphorbiaceae.”
This framework establishes a foundation for drug precursor biosynthesis, terpene pathway engineering, and cultivar development in Euphorbiaceae. By pinpointing cluster structures and tissue-specific expression, genes such as LOC8259981, LOC8259984, and CYP726A enzymes become actionable targets for CRISPR-based pathway enhancement. Species-specific features — such as root-exclusive clusters in V. montana — could guide breeding or metabolic optimization. Beyond Euphorbiaceae, the approach is applicable to other medicinal plants, supporting scalable production of antitumor terpenoids, fragrance compounds, and industrial biomaterials.
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References
DOI
Original Source URL
https://doi.org/10.1093/hr/uhaf097
Funding information
This work was supported by The National Nonprofit Institute Research Grant of CAFINT (No. CAFYBB2023PA005), the National Natural Science Foundation of China (31971685), and the Ten Thousand People Plan of Science and Technology Innovation Leading Talent of Zhejiang, China (No. 2022R52028) awarded to Y.C.
About Horticulture Research
Horticulture Research is an open access journal of Nanjing Agricultural University and ranked number one in the Horticulture category of the Journal Citation Reports ™ from Clarivate, 2023. The journal is committed to publishing original research articles, reviews, perspectives, comments, correspondence articles and letters to the editor related to all major horticultural plants and disciplines, including biotechnology, breeding, cellular and molecular biology, evolution, genetics, inter-species interactions, physiology, and the origination and domestication of crops.