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Differential expression of the TwHMGS gene and its effect on triptolide biosynthesis in Tripterygium wilfordii

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Tong Yuru 1,2,3   Zhang Yifeng 3,4   Zhao Yujun 2   Hu Tianyuan 3,4   Wang Jiadian 3,4   Huang Luqi 1,2 *   Gao Wei 3,4,5  
文摘 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is the first committed enzyme in the MVA pathway and involved in the biosynthesis of terpenes in Tripterygium wilfordii. The full- length cDNA and a 515 bp RNAi target fragment of TwHMGS were ligated into the pH7WG2D and pK7GWIWG2D vectors to respectively overexpress and silence, TwHMGS was overexpressed and silenced in T. wilfordii suspension cells using biolistic-gun mediated transformation, which resulted in 2-fold increase and a drop to 70% in the expression level compared to cells with empty vector controls. During TwHMGS overexpression, the expression of TwHMGR, TwDXR and TwTPS7v2 was significantly upregulated to the control. In the RNAi group, the expression of TwHMGR, TwDXS, TwDXR and TwMCT visibly displayed downregulation to the control. The cells with TwHMGS overexpressed produced twice higher than the control value. These results proved that differential expression of TwHMGS determined the production of triptolide in T. wilfordii and laterally caused different trends of relative gene expression in the terpene biosynthetic pathway. Finally, the substrate acetyl-CoA was docked into the active site of TwHMGS, suggesting the key residues including His247, Lys256 and Arg296 undergo electrostatic or H-bond interactions with acetyl-CoA.
来源 Chinese Journal of Natural Medicines ,2019,17(8):575-584 【核心库】
DOI 10.3724/SP.J.1009.2019.00575
关键词 Overexpression ; RNAi ; HMGS ; Triptolide ; Acetyl-CoA
地址

1. School of Pharmacy Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016  

2. National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700  

3. School of Pharmaceutical Science, Capital Medical University, Beijing, 100069  

4. School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069  

5. Capital Medical University, Beijing Advanced Innovation Center for Human Brain Protection, Beijing, 100069

语种 英文
文献类型 研究性论文
ISSN 2095-6975
学科 生物化学;中国医学
基金 国家自然科学基金 ;  Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education ;  the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan ;  National Program for Special Support of Eminent Professionals ;  Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources
文献收藏号 CSCD:6543711

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