A specific UDP-glucosyltransferase catalyzes the formation of triptophenolide glucoside from Tripterygium wilfordii Hook. f

• Published in: Phytochemistry (Oxford) 2019-10, Vol.166, p.112062-112062, Article 112062
• Main Authors: Ma, Baowei, Liu, Xihong, Lu, Yun, Ma, Xiaochi, Wu, Xiaoyi, Wang, Xing, Jia, Meirong, Su, Ping, Tong, Yuru, Guan, Hongyu, Jiang, Zhouqian, Gao, Jie, Huang, Luqi, Gao, Wei
• Format: Article
• Language: English
• Subjects: Anticancer activity; Docking; Glucosyltransferase TwUGT1; Key amino acid residues; Mutagenesis; Tripterygium wilfordii Hook. f; Triptophenolide 14-O-beta-D-glucopyranoside
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2019.112062

Tripterygium wilfordii Hook. f. is a perennial woody vine member of the Celastraceae family. As a traditional Chinese medicine, it contains complex chemical components and exerts various pharmacological activities. In the present study, we identified a glucosyltransferase, TwUGT1, that can catalyze the synthesis of an abietane-type diterpene glucoside, namely, triptophenolide14-O-beta-D-glucopyranoside, and investigated the pharmacological activity of triptophenolide glucoside in diverse cancer cells. Triptophenolide glucoside exhibited significant inhibitory effects on U87-MG, U251, C6, MCF-7, HeLa, K562, and RBL-2H3 cells as determined by pharmacological analysis. The triptophenolide glucoside content of T. wilfordii was analyzed using Agilent Technologies 6490 Triple Quad LC/MS. The glucosyltransferase TwUGT1 belongs to subfamily 88 and group E in family 1. Molecular docking and site-directed mutagenesis of TwUGT1 revealed that the His30, Asp132, Phe134, Thr154, Ala370, Leu376, Gly382, His387, Glu395 and Gln412 residues play crucial roles in the catalytic activity of triptophenolide 14-O-glucosyltransferase. In addition, TwUGT1 was also capable of glucosylating phenolic hydroxyl groups, such as those in liquiritigenin, pinocembrin, 4-methylumbelliferone, phloretin, and rhapontigenin. [Display omitted] •The specific triptophenolide glucosyltransferase belonged to subfamily 88 and group E in family 1.•Triptophenolide 14-O-beta-D-glucopyranoside is an abietane-type diterpene glucoside, which was discovered in T. wilfordii.•Triptophenolide glucoside exhibited inhibitory effects toward U87-MG, U251, C6, MCF-7, HeLa, K562, and RBL-2H3 cells.•The residues His30, Asp132, Phe134, Thr154, Ala370, Leu376, Gly382, His387, Glu395 and Gln412 of TwUGT1 are crucial roles.