Mining coral-derived terpene synthases and mechanistic studies of the coral biflorane synthase

• DOI: 10.1126/sciadv.adv0805
• Publication Date: 2025-02-26T18:58:46Z
• Authors: Bao Chen; Jingjing Mao; Kangwei Xu; Lijun Liu; Wei Lin; Yue-Wei Guo; Ruibo Wu; Chengyuan Wang; Baofu Xu
• Keywords: Terpene; Cyclopropane; Molecular mechanics

Biflorane diterpenoids are unique natural products often seen in marine animals. Recent studies have reported a small number of biflorane synthases. However, the catalytic mechanism and structural basis for formation remain unclear. To address these issues, we conducted genome mining terpene synthases from sea whip coral Paramuricea clavata , resulting discovery synthase Pc TS1. We performed series isotope labeling, crystallography, quantum mechanics/molecular mechanics calculations, mutagenesis toward TS1 to investigate mechanism. Isotopic labeling studies, together with elucidate cascade 1,10-cyclization, 1,3-hydride shift, 1,6-cyclization, 1,2-hydride 2,6-cyclization, cyclopropane ring opening, deprotonation by generated pyrophosphate, forming scaffold. Crystallography, mechanics, confirmed produced different scaffolds. Our work demonstrated formation, elucidated second crystal structure synthase, realized skeleton expansion.