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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Structurally diverse diterpenoids from Euphorbia milii: Discovery and RORγt-binding evaluation
Meng-Yuan Dai1, Xue-Li Hu1, Wen-Chang Li1
1Yunnan Key Laboratory of Genetic Improvement of Herbal Oil Crops, Industrial Crops Research Institute, Yunnan Academy of Agricultural Sciences, Kunming, 650225, PR China.
None:
Ten previously undescribed diterpenoids (1-10), representing four diverse architectural types, along with eight known analogs (11-18), were isolated from Euphorbia milii. Compounds 1-3 were characterized as ent-atisane diterpenoids, with 1 and 2 featuring a C-19-nor- and a 3,4-seco-19-nor-ent-atisane framework, respectively, and their plausible biosynthetic pathways were proposed. The remaining new isolates were established to be ent-pimarane (4-7), ent-abietane (8 and 9), and ent-verticillane (10) diterpenoids. Binding affinity assays revealed that compounds 6, 7, and 14 bound directly to retinoic acid-related orphan receptor γt (RORγt), of which 14 demonstrated the highest affinity (Kd = 4.2 × 10-5 M) and significantly suppressed Th17 cell differentiation.
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