Unlocking safflower’s secrets: Scientists identify key gene in flavonoid glycoside biosynthesis

Safflower is widely valued for its flavonoid glycosides, particularly for cardiovascular therapeutics and natural dyes. However, the biosynthetic mechanism of these bioactive compounds has long remained elusive. In this study, researchers applied a genome-wide screening and multi-omics strategy to identify the critical genes responsible for flavonoid glycoside biosynthesis in safflower. They focused on the CYP and UGT gene families and ultimately discovered a key glycosyltransferase, CtOGT1, which catalyzes glycoside production from multiple flavonoid substrates. Functional validation through molecular docking, expression profiling, and enzymatic assays confirmed CtOGT1's high specificity and activity. These findings provide valuable insights into plant metabolite biosynthesis and offer a robust foundation for metabolic engineering of safflower and related crops.

Safflower (Carthamus tinctorius L.) has been cultivated for over 4,500 years and is a staple in traditional medicine and natural dye industries. Its medicinal value largely stems from flavonoid glycosides like hydroxysafflor yellow A (HSYA), known for treating stroke and heart disease. While the biosynthetic pathways of flavonoids are partially understood in model plants, safflower's unique chalcone-derived glycosides remain under-characterized. Traditional approaches to gene discovery often rely on homology-based inference, which limits species-specific resolution. Advances in genomics and omics integration offer opportunities to uncover functional genes directly within the target species. Due to these challenges, a systematic and high-resolution study is required to uncover the genes regulating flavonoid glycoside biosynthesis in safflower.

A research team from Chengdu University of Traditional Chinese Medicine has published a new study (DOI: 10.1093/hr/uhae261) on September 16, 2024, in Horticulture Research, unveiling the key gene behind safflower's bioactive flavonoid glycosides. Using a genome-wide and multi-omics framework, the team identified CtOGT1 as a glycosyltransferase that drives the biosynthesis of flower-specific compounds. The work integrates gene family analysis, transcriptomics, metabolomics, and molecular validation to pinpoint and verify this crucial enzyme, shedding light on how safflower produces its potent medicinal compounds.

The team initiated their study by cataloging 264 cytochrome P450 (CYP) and 140 UDP-glycosyltransferase (UGT) genes from the safflower genome. By analyzing their evolutionary relationships, gene structures, motifs, chromosomal locations, and promoter cis-elements, researchers shortlisted candidates potentially involved in flavonoid glycoside synthesis. Through multi-omics integration—including transcriptome data from various tissues, developmental stages, and MeJA treatment—they correlated gene expression with metabolite accumulation. Notably, HSYA was found to be synthesized exclusively in safflower flowers. Among the candidates, CtOGT1 emerged as a key enzyme based on its expression profile and phylogenetic similarity to known 7-O-glycosyltransferases. Functional validation was performed using both Nicotiana benthamiana infiltration and prokaryotic expression systems. These assays confirmed CtOGT1's activity in converting flavonoids like apigenin and scutellarein into their 7-O-glycosylated forms. Kinetic analyses further demonstrated that CtOGT1 exhibits strong substrate affinity, with Km values ranging from 32.93 to 74.16 μM depending on the flavonoid. This comprehensive approach successfully identified CtOGT1 as a critical regulator in safflower’s flavonoid glycoside biosynthesis.

“This discovery marks a significant step forward in our understanding of how safflower produces its most potent bioactive compounds,” said Dr. Jin Pei, corresponding author of the study. “The identification and validation of CtOGT1 provide not only a vital genetic tool for improving safflower quality through breeding and biotechnology but also a model for studying glycosylation mechanisms in other medicinal plants. Our work demonstrates the power of integrating genomics with functional assays to decode complex plant metabolic networks.”

The discovery of CtOGT1 paves the way for metabolic engineering of safflower to enhance the yield and quality of medicinal flavonoid glycosides. This gene could serve as a target for precision breeding strategies aimed at improving cardiovascular therapies derived from traditional Chinese medicine. Beyond safflower, the approach employed in this study—combining genome-wide screening with multi-omics integration—can be applied to uncover key metabolic genes in other economically valuable plants. Future research may explore the regulatory networks involving CtOGT1 and extend to synthetic biology platforms to produce flavonoid glycosides in microbial or heterologous systems for scalable pharmaceutical production.

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References

DOI

10.1093/hr/uhae261

Original Source URL

https://doi.org/10.1093/hr/uhae261

Funding information

This work was supported by grants from the National Natural Science Foundation of China (82274039; 82404792), Science and Technology Department of Sichuan Province (2021YFYZ0012-5), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202209), Natural Science Foundation of Sichuan Province (2023NSFSC0660; 2023NSFSC1770) and the Xinglin Talent Program of Chengdu University of (TCMQJJJ2023010; QJRC2021011).

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.