Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of
Journal or Book Title
The medicinal plant Salvia miltiorrhiza produces various tanshinone diterpenoids that have pharmacological activities such as vasorelaxation, against ischemia-reperfusion injury, and antiarrhythmic effects. Their biosynthesis is initiated from the general diterpenoid precursor (E,E,E)-geranylgeranyl diphosphate by sequential reactions catalyzed by copalyl diphosphate synthase (CPS) and kaurene synthase-like (KSL) cyclases. Here is reported characterization of these enzymatic families from S. miltiorrhiza, which has led to the identification of novel pathways, including roles for separate CPSs in tanshinone production in roots versus aerial tissues (SmCPS1 and SmCPS2, respectively), as well as the novel production of ent-13-epi-manoyl oxide by SmCPS4 and SmKSL2 in floral sepals. The conserved SmCPS5 is involved in gibberellin plant hormone biosynthesis. Down-regulation of SmCPS1 by RNAi resulted in substantial reduction of tanshinones, and metabolomics analysis revealed 21 potential intermediates, indicating a complex network for tanshinone metabolism defined by certain key biosynthetic steps. Notably, the correlation between conservation pattern and stereochemical product outcome of the CPSs observed here, suggests a degree of correlation that, especially when combined with the identity of certain key residues, may be predictive. Accordingly, this study provides molecular insights into the evolutionary diversification of functional diterpenoids in plants.
American Society of Plant Biologists
Cui, Guanghong; Duan, Lixin; Jin, Baolong; Qian, Jun; Xue, Zheyong; Shen, Guoan; Hugh Snyder, John; Song, Jingyuan; Chen, Shilin; Huang, Luqi; Peters, Reuben J.; and Qi, Xiaoquan, "Functional Divergence of Diterpene Syntheses in the Medicinal Plant Salvia miltiorrhiza" (2015). Biochemistry, Biophysics and Molecular Biology Publications. 92.