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Updated: Jun 3, 2025

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
From Monocyclization to Pentacyclization: A Versatile Plant Cyclase Produces Diverse Sesterterpenes with Anti-Liver
Kai Guo1, Xue Tang1, Yan-Chun Liu2
1State Key Laboratory of Southwestern Chinese Medicine Resources, and Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. China.
Abstract:
A prolific multi-product sesterterpene synthase CbTPS1 is characterized from the medicinal Brassicaceae plant Capsella bursa-pastoris. Twenty different sesterterpenes including 16 undescribed compounds, possessing 10 different mono-/di-/tri-/tetra-/penta-carbocyclic skeletons, including the unique 15-membered macrocyclic and 24(15→14)-abeo-capbuane scaffolds, are isolated and structurally elucidated from engineered Escherichia coli strains expressing CbTPS1. Site-directed mutagenesis assisted by molecular dynamics simulations resulted in the variant L354M with up to 13.2-fold increased sesterterpene production. These structurally diverse products suggest a comprehensive cyclization mechanism for plant sesterterpenes and provide compelling evidence for the initial cyclization of geranylfarnesyl diphosphate via a crucial 15-membered monocyclic carbocation. The activities of these sesterterpenes against liver fibrosis is inferred from the inhibition of the transforming growth factor-β/Smad signaling pathway and collagen synthesis. These findings greatly expand the chemical space and biological functions of sesterterpenes and provide new insights into the catalytic mechanism of terpene synthases.
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