The complete synthetic pathway of echinacoside from Cistanche deserticola and its de novo biosynthesis in yeast

Yali Ban; Jixuan Jiang; Hongwang Yang; Haiyang Jia; Yaru Pang; Xu Cheng; Jianbin Yan; Qinggang Liao; Chun Li; Bo Lv; Yongjun Feng

doi:10.1016/j.xplc.2025.101430

The complete synthetic pathway of echinacoside from Cistanche deserticola and its de novo biosynthesis in yeast

Plant Commun. 2025 Jun 24:101430. doi: 10.1016/j.xplc.2025.101430. Online ahead of print.

Authors

Yali Ban¹, Jixuan Jiang¹, Hongwang Yang¹, Haiyang Jia², Yaru Pang², Xu Cheng², Jianbin Yan³, Qinggang Liao³, Chun Li⁴, Bo Lv⁵, Yongjun Feng⁶

Affiliations

¹ School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
² Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology/Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
³ Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, China.
⁴ Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology/Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China; Key Lab for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China. Electronic address: lichun@tsinghua.edu.cn.
⁵ Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology/Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China. Electronic address: lichun@tsinghua.edu.cn.
⁶ School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Electronic address: lichun@tsinghua.edu.cn.

PMID: 40566684
DOI: 10.1016/j.xplc.2025.101430

Abstract

Echinacoside (ECH), a representative phenylethanol glycoside, possesses diverse pharmacological properties and has been employed in the treatment of neurodegenerative disorders (e.g., Parkinson's and Alzheimer's diseases), ischemic brain injury, and cancer. The growing therapeutic demand for ECH has highlighted the need for scalable production. However, conventional methods face significant challenges: chemical synthesis is hindered by the compound's structural complexity, while plant extraction is limited by the low natural yield of ECH from Cistanche deserticola, a parasitic desert plant with host-dependent growth. To establish a sustainable microbial biosynthesis platform, we first deciphered the biosynthetic pathway of ECH in C. deserticola by integrating metabolomic analyses of plant tissues and callus cultures. This enabled the identification of key precursors, enzymatic steps, and regulatory mechanisms. Leveraging this knowledge, we engineered Saccharomyces cerevisiae for de novo ECH production by reconstructing the heterologous pathway, achieving a titer of 7.52 ± 1.42 mg/L. Our study not only provides a foundation for the industrial-scale production of ECH but also deepens the understanding of bioactive compound biosynthesis in parasitic plants, offering insights for future pathway engineering efforts.

Keywords: Cistanche deserticola; Differential gene analysis; Echinacoside; Metabolomics; Microbial biomanufacturing.