Safflower has been used in traditional Chinese medicine for over two thousand years to promote blood circulation, yet the genetic machinery behind its most valuable medicinal compounds has remained largely mysterious. Now, researchers have pinpointed a key enzyme that drives the production of hydroxysafflor yellow A (HSYA)—a compound with proven cardiovascular and cerebrovascular benefits—by comparing yellow and white safflower varieties. Their findings reveal how a single glycosyltransferase enzyme can make the difference between a flower rich in therapeutic compounds and one that produces none.
Safflower comes in many colors, and those colors are more than just aesthetics—they reflect dramatic differences in chemical composition. Yellow safflower varieties are packed with hydroxysafflor yellow A (HSYA) and other chalcone glycosides, while white varieties contain little to none of these compounds but accumulate other flavonoids instead. Despite safflower's long history of medicinal use, the genes controlling these color-associated metabolic differences have been difficult to pin down, largely because flavonoid biosynthesis involves a complex network of enzymes and regulatory factors rather than a single genetic switch. Based on these challenges, the team set out to conduct an in-depth investigation of the genetic and molecular mechanisms underlying safflower color and flavonoid glycoside production.
Now, a team led by Professor Meili Guo at Naval Medical University in Shanghai, together with collaborators from Bengbu Medical University and Shanghai University, has published (DOI: 10.1093/hr/uhag068) a comprehensive multi-omics study in Horticulture Research (March 4, 2026) that identifies the key genes responsible for yellow coloration and HSYA biosynthesis in safflower. By integrating bulk segregation analysis sequencing (BSA-seq), transcriptomics, and metabolomics, the researchers mapped five quantitative trait loci (QTL) regions across safflower chromosomes and zeroed in on a family of glycosyltransferase enzymes—with one particular enzyme, CtUGT52 , emerging as the central player.
The team started with two extreme safflower lines: ZHH0119, a yellow variety rich in HSYA, and XHH007, a white variety that produces no HSYA but high levels of another flavonoid called nicotiflorin. After crossing the two parents and generating an F4 population, they constructed near-isogenic gene pools representing the two extreme color traits. BSA-seq analysis localized five QTL regions on chromosomes 2, 8, 9, 10, and 12, harboring 6 CtPALs , 3 CtC4Hs , 2 Ct4CLs , 1 CtCH S, 32 CtUGTs , and 70 CtCYPs —all tied to the yellow phenotype. Transcriptomic profiling across multiple flowering stages revealed that 48 CtUGTs and 51 CtCYPs were significantly upregulated in yellow compared to white safflower. Integrated metabolomic analysis then narrowed the field to eight CtUGT genes (CtUGT50–57) that showed strong positive correlations with chalcone glycoside accumulation. When the researchers expressed these enzymes in E. coli and tested them against various flavonoid substrates, CtUGT52 stood out for its remarkable versatility: it could glycosylate chalcones, flavonols, and flavones alike, producing both mono- and diglycosides. Transgenic safflower plants overexpressing CtUGT52 produced 2 to 3.8 times more HSYA than wild-type plants, confirming the enzyme's central role in HSYA biosynthesis. Site-directed mutagenesis further revealed the key amino acid residues—S277 and Q335 for phloretin, Q335 and E358 for kaempferol, and P162 and E213 for luteolin—that govern CtUGT52' s interactions with different substrates.
The authors said, "We were surprised to find that a single glycosyltransferase could be so versatile— CtUGT52 doesn't just pick one type of flavonoid to work on; it handles chalcones, flavonols, and flavones with equal ease, producing both mono- and diglycosides. That kind of catalytic promiscuity is rare and tells us this enzyme sits at a critical hub in safflower's flavonoid network. When we overexpressed it in transgenic plants, HSYA levels jumped several-fold, which really drove home its importance." They added, "Understanding how CtUGT52 recognizes different substrates at the molecular level gives us a roadmap for engineering even better versions of this enzyme—potentially for producing high-value medicinal compounds more efficiently."
The discovery opens new doors for safflower breeding and metabolic engineering. Breeders can now use CtUGT52 as a molecular marker to select for yellow varieties with high HSYA content, accelerating the development of superior medicinal safflower lines. Beyond agriculture, the enzyme's broad substrate tolerance makes it a promising biocatalyst for industrial production of flavonoid glycosides—compounds with growing demand in pharmaceuticals, nutraceuticals, and cosmetics. The study also provides a blueprint for using multi-omics approaches to dissect complex metabolic traits in other medicinal plants, potentially unlocking a wealth of therapeutic compounds that have remained genetically inaccessible until now.
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References
DOI
Original Source URL
https://doi.org/10.1093/hr/uhag068
Funding information
This work was supported by the National Natural Science Foundation of China (81973421) and the National Key R&D Program of China (2019YFC1711100).
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.
Horticulture Research
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BSA-seq integrated with transcriptomics and metabolomics revealing the candidate genes associated with safflower colors and flavonoid glycosides biosynthesis
4-Mar-2026
The authors declare that they have no competing interests.