KAIST Elucidates Biosynthetic Pathway of Anticancer Compounds in Lespedeza cuneata

The biosynthetic pathway of anticancer compounds in the native medicinal plant Lespedeza cuneata, known in Korean as Gwangdaessari, has been identified. Lespedeza cuneata is a shrub that can be easily found in Korea, and its leaves and roots have long been used as medicinal ingredients in Northeast Asia. In particular, this plant contains a variety of alkaloids, including securinine, giving it strong potential for new drug development. However, alkaloids are known to have highly complex structures, making it difficult to elucidate their biosynthetic pathways.

KAIST announced on the 6th that a research team led by Professor Kim Sangkyu of the Department of Biological Sciences and a research team led by Professor Han Sungkyu of the Department of Chemistry have identified the key steps by which securinine-type compounds with anticancer effects are produced in Lespedeza cuneata.

(From left) Professor Kim Sanggyu, Professor Han Sunggyu. KAIST

It is not new that medicinal ingredients are derived from plants. What has remained an unresolved question is how plants actually produce the compounds that can be used as drugs. The biosynthetic pathway of securinine-type compounds in Lespedeza cuneata was no exception.

Securinine was first discovered in Lespedeza cuneata in 1956, and more than 130 related compounds have been reported to date. Some of these are known to exhibit anticancer effects or to help regenerate neural tissue in the brain. However, the process by which anticancer effects and related activities arise in Lespedeza cuneata has remained unknown for the past 70 years.

The shrouded biosynthetic pathway underlying the anticancer effects of Lespedeza cuneata was uncovered through collaboration between chemistry and biological sciences. The joint research brought together Professor Han's team, which has long studied the chemical synthesis of securinine-type compounds, and Professor Kim's team, which specializes in plant genomics and single-cell analysis.

Professor Kim's team first collected Lespedeza cuneata from the KAIST Ecological Forest in the Bulgoksan area of Seongnam to prepare research samples, and then carried out high-resolution genomic analysis of the plant. Focusing in particular on leaf tissues where securinine production is active, they performed single-cell transcriptome analysis to closely track which genes are active in which cells.

In the joint study, Professor Han's team identified virosine B as the immediate precursor to securinine. They then synthesized virosine B directly in the laboratory and monitored its transformation, revealing that an enzyme in the plant called sulfotransferase plays a key role in converting virosine B into securinine, the active anticancer ingredient.

This is the first finding to show that sulfotransferase does more than simply attach chemical groups as a supporting modification; it also plays an important role in altering the very structure of alkaloids.

AI-generated image. Korea Advanced Institute of Science and Technology

The joint research team expects that this achievement will open the way to stable production of anticancer compounds in laboratories and microbial factories.

Professors Kim and Han said, "This study is a case where we have elucidated at the molecular level how high value-added natural products obtainable from native Korean plants are synthesized," adding, "The significance of this work lies in having laid the foundation for stable production of anticancer compounds using microbes and cells, and for enabling diverse pharmaceutical and medical applications."

Meanwhile, this study also involved KAIST postdoctoral researchers Jung Sungjun and Kang Kyumin, and integrated M.S.-Ph.D. program student Kim Taein as co-first authors. The research results were recently featured in the international journal Nature Communications.

This content was produced with the assistance of AI translation services.