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Peer-reviewedCC BY 4.0Frontiers in Plant Science

Friedelin in plants: metabolism, synthase engineering and production strategies

  1. 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University
  2. 2State Key Laboratory of Rice Biology and Breeding, Northern Center of China National Rice Research Institute, China National Rice Research Institute

Abstract

Friedelin (FD) is a pentacyclic triterpenoid with significant pharmacological potential and serves as the biosynthetic precursor to the anti-obesity drug celastrol. Despite its value, FD availability is limited by low natural abundance and the stereochemical complexity of chemical synthesis. This article critically reviews the state-of-the-art in FD research, spanning natural distribution, extraction methodologies, and the molecular basis of its biosynthesis. The structural evolution of friedelin synthases (FDSs), contrasting the mechanisms of multifunctional versus single-function enzymes, was analyzed. Furthermore, a comprehensive roadmap for sustainable production, integrating “Push-Block-Regulate-Store” metabolic engineering strategies with novel insights into transcriptional regulation, was provided. It is proposed that the convergence of AI-driven enzyme design, transporter engineering, and CRISPR-based precision breeding will overcome current yield bottlenecks, enabling the industrial-scale biomanufacturing of FD and its derivatives.

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BibTeX
@article{cui2026friedelin,
  title = {{Friedelin in plants: metabolism, synthase engineering and production strategies}},
  author = {Qi Cui and Chenglin Shi and Qiannan Li and Junyu Chen and Zheyong Xue and Xiaoxia Shen and Juzhao Liu},
  journal = {Frontiers in Plant Science},
  year = {2026},
  month = nov,
  doi = {10.3389/fpls.2026.1890611},
  url = {https://www.frontiersin.org/articles/10.3389/fpls.2026.1890611/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Friedelin in plants: metabolism, synthase engineering and production strategies
AU  - Qi Cui
AU  - Chenglin Shi
AU  - Qiannan Li
AU  - Junyu Chen
AU  - Zheyong Xue
AU  - Xiaoxia Shen
AU  - Juzhao Liu
PY  - 2026
DA  - 2026/11/02
JO  - Frontiers in Plant Science
DO  - 10.3389/fpls.2026.1890611
UR  - https://www.frontiersin.org/articles/10.3389/fpls.2026.1890611/full
AB  - Friedelin (FD) is a pentacyclic triterpenoid with significant pharmacological potential and serves as the biosynthetic precursor to the anti-obesity drug celastrol. Despite its value, FD availability is limited by low natural abundance and the stereochemical complexity of chemical synthesis. This article critically reviews the state-of-the-art in FD research, spanning natural distribution, extraction methodologies, and the molecular basis of its biosynthesis. The structural evolution of friedelin synthases (FDSs), contrasting the mechanisms of multifunctional versus single-function enzymes, was analyzed. Furthermore, a comprehensive roadmap for sustainable production, integrating “Push-Block-Regulate-Store” metabolic engineering strategies with novel insights into transcriptional regulation, was provided. It is proposed that the convergence of AI-driven enzyme design, transporter engineering, and CRISPR-based precision breeding will overcome current yield bottlenecks, enabling the industrial-scale biomanufacturing of FD and its derivatives.
SN  - 1664-462X
ER  -