Natural Products & Plant Materials
Four Key Enzymes Found for HSYA, a Stroke Drug Candidate Unique to Safflower
Researchers at Peking University identified four enzymes for the biosynthesis of HSYA, a component found only in safflower flowers, and synthesized it from scratch in a relative of tobacco.
The biosynthetic pathway of hydroxysafflor yellow A (HSYA), a yellow pigment found only in the flowers of safflower (Carthamus tinctorius), has been uncovered. HSYA is in clinical development as a candidate treatment for acute ischemic stroke, and it has a distinctive structure in which two sugars are attached to a quinochalcone backbone by carbon-carbon bonds. Researchers at the School of Pharmaceutical Sciences, Peking University, reported the results in Nature Communications.
Four enzymes from naringenin to HSYA
The researchers found four enzymes. CtF6H adds a hydroxyl group at position 6 of the flavonoid naringenin to make carthamidin, and CtCHI1 handles the isomerization between carthamidin and isocarthamidin. The C-glycosyltransferase CtCGT and the oxidase Ct2OGD1 then act together to complete HSYA. The researchers cross-checked each function using VIGS (virus-induced gene silencing) experiments, which suppress gene expression in safflower, de novo synthesis in Nicotiana benthamiana, semi-synthesis in yeast and in vitro enzyme assays.
The researchers explained that HSYA is made only when the four genes are highly expressed together and the gene for flavanone 2-hydroxylase (F2H) is absent. This is their explanation for why the compound is not found in other plants.
This study uncovered the biosynthetic pathway and did not newly test HSYA's effect in treating stroke. Some of the researchers stated that they have filed related patents.
- Four enzymes, CtF6H, CtCHI1, CtCGT and Ct2OGD1, convert naringenin into HSYA
- Functions cross-validated with VIGS, de novo synthesis in plants, yeast semi-synthesis and in vitro assays
- High expression of the four genes and absence of the F2H gene proposed as conditions for safflower specificity
Limitations This study elucidated a biosynthetic pathway and did not test therapeutic effects. Some authors are applicants on related patents.
Original Research
- Wang ZL, et al. · Peking University. Elucidation of the biosynthetic pathway of hydroxysafflor yellow A. Nature Communications. DOI: 10.1038/s41467-025-59774-3
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