From Monocyclization to Pentacyclization: A Versatile Plant Cyclase Produces Diverse Sesterterpenes with Anti‐Liver Fibrosis Potential

• DOI: 10.1002/advs.202415370
• Publication Date: 2025-01-10T18:12:02Z
• Authors: Kai Guo; Xue Tang; Yan‐Chun Liu; Hui‐Zhen Cheng; Huan Liu; Yu‐Zhou Fan; Xiao‐Yu Qi; Rui Xu; Juan‐Juan Kang; De‐Sen Li; Guo‐Dong Wang; Jonathan Gershenzon; Yan Liu; Sheng‐Hong Li
• Keywords: Terpene

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 mono‐/di‐/tri‐/tetra‐/penta‐carbocyclic skeletons, unique 15‐membered macrocyclic and 24(15→14)‐ abeo ‐capbuane scaffolds, are isolated structurally elucidated engineered Escherichia coli strains expressing CbTPS1. Site‐directed mutagenesis assisted by molecular dynamics simulations resulted in variant L354 M with up to 13.2‐fold increased production. These diverse products suggest a comprehensive cyclization mechanism for provide compelling evidence initial of geranylfarnesyl diphosphate via crucial monocyclic carbocation. The activities these against liver fibrosis inferred inhibition transforming growth factor‐β/Smad signaling pathway collagen synthesis. findings greatly expand chemical space biological functions new insights into catalytic terpene synthases.