One enzyme, many sugars: How a single protein builds a medicinal plant’s chemical arsenal

For centuries, Epimedium has been used in traditional medicine to support bone health and vitality, yet the precise location of its active compounds within the plant—and the enzymes that create them—has remained a mystery. Now, researchers have mapped where these medicinal molecules accumulate and identified a single enzyme capable of producing a remarkable diversity of flavonol glycosides from multiple substrates and sugar donors. The findings open new doors for understanding how plants manufacture their chemical defenses and for engineering these pathways to produce valuable therapeutics more efficiently.

Plants produce flavonoids—bioactive compounds with antioxidant, anti-inflammatory, and osteoprotective properties—through complex modification pathways. Glycosylation, the attachment of sugar molecules to flavonoid cores, is a key driver of this chemical diversity. In Epimedium, over 88% of kaempferol derivatives are glycosylated, yet the enzymes responsible and their spatial regulation within the plant have been poorly understood. Due to these challenges, the researchers set out to systematically investigate both where these compounds accumulate and which genes orchestrate their structural variation.

Now, researchers from the South China Botanical Garden, Chinese Academy of Sciences, and collaborating institutions have published (DOI: 10.1093/hr/uhag187) their findings in Horticulture Research on May 8, 2026. Using MALDI-TOF mass spectrometry imaging, combined with metabolomic and transcriptomic profiling, the team visualized the spatial distribution of four key marker compounds—epimedin A, B, C, and icariin—and identified a single glycosyltransferase, UGT72B113, as a major driver of flavonol diversity in Epimedium sagittatum.

The study revealed that epimedin C and icariin—the two most abundant marker compounds—accumulate predominantly in the non-vein mesophyll of leaves, with significantly lower concentrations in the main leaf veins. This spatial heterogeneity was confirmed by both mass spectrometry imaging and tissue-dissected HPLC analysis, demonstrating that these compounds are stored locally rather than uniformly distributed. To uncover the genetic basis of this chemical diversity, the researchers performed transcriptomic sequencing across leaves, stems, and rhizomes, identifying 96 UGT genes. Among them, five were highly expressed across all three tissues. When expressed as recombinant proteins and tested in vitro, UGT72B113 stood out for its extraordinary catalytic versatility: it accepted multiple kaempferol-type aglycones—including kaempferol, kaempferide, and 8-prenylkaempferol—and utilized UDP-glucose, UDP-rhamnose, UDP-xylose, and UDP-galactose as sugar donors. Remarkably, from a single substrate, the enzyme generated mono-, di-, and even triglycosylated products, with kaempferide showing the highest substrate preference (Kₘ = 4.51 μM). Structural modeling suggested that UGT72B113’s constrained active pocket may allow distinct substrate binding orientations, enabling the production of multiple regioisomeric products from one molecule.

“We were genuinely surprised by how much chemistry one enzyme could do,” the authors said. “UGT72B113 doesn't just accept a few substrates—it works with multiple sugar donors and builds different glycosidic linkages on the same molecule. That kind of flexibility is rare, and it explains, at least in part, why Epimedium produces such a rich arsenal of flavonol glycosides.” They added that the enzyme's ability to generate both mono- and multi-glycosylated products from a single starting material suggests it plays a central role in shaping the plant's medicinal chemistry.

The findings have practical implications for both traditional medicine and biotechnology. By identifying where active compounds accumulate, the study provides guidance for optimizing harvest and processing practices—suggesting that non-vein leaf tissue may be the most valuable medicinal material. More broadly, UGT72B113’s broad substrate promiscuity and sugar donor flexibility make it a promising biocatalyst for synthetic biology applications. The enzyme could be harnessed to produce diverse flavonol glycosides in engineered microbial systems, offering a sustainable alternative to plant extraction for pharmaceutical production. As the demand for plant-derived therapeutics continues to grow, enzymes like UGT72B113 represent powerful tools for accessing nature’s chemical diversity with precision and efficiency.

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References

DOI

10.1093/hr/uhag187

Original Source URL

https://doi.org/10.1093/hr/uhag187

Funding information

National Natural Science Foundation of China (32570446); Guangdong Basic and Applied Basic Research Foundation (2023A1515012007).

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.