The Oplopanax elatus genome reveals dammaradienol synthase evolution enabling reconstruction of RK type ginsenosides biosynthesis

RK-type ginsenosides are a subgroup of dehydrated dammarane saponins with valuable bioactivities, but they are not naturally produced in cultivated ginseng. The ginseng relative Oplopanax elatus accumulates dammaradienol, the precursor scaffold of RK-type ginsenosides, but does not produce RK-type ginsenosides. Here, we identify OeOSC14 as a specialized dammaradienol synthase that evolved through duplication and neofunctionalization of an ancestral multifunctional triterpene synthase by combining chromosome-level genome assembly, comparative genomics and biochemical analyses. Consistent with this evolutionary transition, a single N260Y substitution converts OeOSC14 from a dammaradienol-specific enzyme back into a multifunctional triterpene synthase. We further show that loss of functional C12 hydroxylase blocks the downstream oxidative step required for RK-type ginsenoside biosynthesis in O. elatus. Reconstitution of the pathway in Nicotiana benthamiana enables de novo production of ginsenosides Rk1, Rk2, and Rk3, providing evolutionary insight into triterpene diversification and establishing a plant-based route for producing these compounds.

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Journal
Nature Communications
Published
2026-06-24
DOI
https://doi.org/10.1038/s41467-026-74686-6
Primary Topic
Ginseng Biological Effects and Applications
Type
article
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article

The Oplopanax elatus genome reveals dammaradienol synthase evolution enabling reconstruction of RK type ginsenosides biosynthesis

Hailong Shen, Yangxin Wang, Xin Hua, Peng Zhang et al.
Nature Communications
Ginseng Biological Effects and Applications
article

The Oplopanax elatus genome reveals dammaradienol synthase evolution enabling reconstruction of RK type ginsenosides biosynthesis

Hailong Shen, Yangxin Wang, Xin Hua, Peng Zhang, Zeyu An, He Zhang, Zhong‐Jian Liu, Jie Zhang, 康梦影, Dongran Zheng, Zhichao Xu, Yuxin Song, Wanjie Xue, Yuhua Li, Yue Wang, Shuping Zhou, Saneyuki Kawabata, Chang Yang, Wei Song, Zhuo Zhang, Xin Wang, Yang Zhang, Hao Wu, Chang Li
article en

Abstract

RK-type ginsenosides are a subgroup of dehydrated dammarane saponins with valuable bioactivities, but they are not naturally produced in cultivated ginseng. The ginseng relative Oplopanax elatus accumulates dammaradienol, the precursor scaffold of RK-type ginsenosides, but does not produce RK-type ginsenosides. Here, we identify OeOSC14 as a specialized dammaradienol synthase that evolved through duplication and neofunctionalization of an ancestral multifunctional triterpene synthase by combining chromosome-level genome assembly, comparative genomics and biochemical analyses. Consistent with this evolutionary transition, a single N260Y substitution converts OeOSC14 from a dammaradienol-specific enzyme back into a multifunctional triterpene synthase. We further show that loss of functional C12 hydroxylase blocks the downstream oxidative step required for RK-type ginsenoside biosynthesis in O. elatus. Reconstitution of the pathway in Nicotiana benthamiana enables de novo production of ginsenosides Rk1, Rk2, and Rk3, providing evolutionary insight into triterpene diversification and establishing a plant-based route for producing these compounds.

Nature Communications
Harbin Medical University (CN), State Forestry and Grassland Administration (CN), Northeast Forestry University (CN), Fujian Agriculture and Forestry University (CN), The University of Tokyo (JP)
Openalex Percentile: Top 11%
Ginseng Biological Effects and Applications
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