Search

A sesquiterpene synthase gene was identified from the transcriptome of Euphorbia fischeriana Steud, and the function of its product EfTPS12 was characterized by in vitro biochemical experiments and synthetic biology approaches. EfTPS12 catalyzed conversion of farnesyl diphosphate into three products, including cedrol (1) and eupho-acorenols A (2) and B (3) (two diastereoisomers of tricho-acorenol), thereby being named EfCAS herein. The structures of 2 and 3 were determined by spectroscopic methods and comparison of experimental and calculated electronic circular dichroism spectra. EfCAS is the first example of a plant-derived sesquiterpene synthase that is capable of synthesizing acorane-type alcohols. This study also documents that synthetic biology approaches enable large-scale preparation of volatile terpenes and thereby substantially facilitate characterization of corresponding terpene synthases and elucidation of the structures of their products.

Glioblastoma (GBM) is a common and aggressive brain tumor with a median survival of 12-15 months. Temozolomide (TMZ) is a first-line chemotherapeutic agent used in GBM therapy, but the occurrence of drug resistance limits its antitumor activity. The natural compound cedrol has remarkable antitumor activity and is derived from Cedrus atlantica. In this study, we investigated the combined effect of TMZ and cedrol in GBM cells in vitro and in vivo. The TMZ and cedrol combination treatment resulted in consistently higher suppression of cell proliferation via regulation of the AKT and MAPK signaling pathways in GBM cells. The combination treatment induced cell cycle arrest, cell apoptosis, and DNA damage better than either drug alone. Furthermore, cedrol reduced the expression of proteins associated with drug resistance, including O6-methlyguanine-DNA-methyltransferase (MGMT), multidrug resistance protein 1 (MDR1), and CD133 in TMZ-treated GBM cells. In the animal study, the combination treatment significantly suppressed tumor growth through the induction of cell apoptosis and decreased TMZ drug resistance. Moreover, cedrol-treated mice exhibited no significant differences in body weight and improved TMZ-induced liver damage. These results imply that cedrol may be a potential novel agent for combination treatment with TMZ for GBM therapy that deserves further investigation.

Chemical investigation of the tubers of Sinningia allagophylla led to the isolation of two new chromenes, (2S)-12-hydroxylapachenole (1) and (3R)-3,4-dihydro-3-hydroxy-4-oxo-8-methoxylapachenole (2), and three new dimeric chromenes, allagophylldimers A-C (3-5). Thirteen known compounds, 6-methoxy-7,8-benzocoumarin (6), lapachenole, 8-methoxylapachenole, tectoquinone, 7-hydroxytectoquinone, dunniol, α-dunnione, dunnione, 8-hydroxydunnione, aggregatin E, cedrol, oleanolic acid, and halleridone, were also identified. 6-Methoxy-7,8-benzocoumarin (6) has been isolated for the first time from a natural source.

(+)-Cedrol [1] was biotransformed by cultures of Steptomyces griseus ATCC10137 and Bacillus cereus UI 1477 (NRRL B-14591). Metabolites isolated by solvent extraction and chromatography over Si gel and reversed-phase RP-C 18 columns and by preparative tlc, were examined by ms and 1 H-and 13 C-nmr spectroscopy. B.cereus afforded 2S-hydroxycedrol [2] as the only metabolite