[Effects of fosmidomycin and lovastatin treatment on taxol biosynthesis in suspension culture cells of Taxus chinensis].
There is a dichotomy in the biosynthetic pathway of terpenoid precursor isopentenyl diphosphate (IPP) in higher plant. One is the classical mevalonate pathway in cytosol, and the other is non-mevalonate pathway in plastid. To know the origin of the taxane ring system of taxol in suspension culture of Taxus chinensis, lovastatin and fosmidomycin were used to block the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) and 1-deoxy-D-xylulose-5-phosphate reducto-isomerase (DXR) in the mevalonate and non-mevalonate branch respectively of the terpenoid biosynthetic pathway. Methyl jasmonate (MJ) was used to improve the biosynthesis of taxol. Taxol content was determined by HPLC, the transcriptional expression of genes encoding DXR and HMGR were investigated by real time PCR. Taxol production was lowered by about 2/5 and 1/5 by fosmidomycin (200 mmol/L) and fosmidomycin (200 mmol/L)+MJ (100 mmol/L) treatment respectively, and was lowered by about 1/6 and 1/10 by lovastatin (1 mmol/L) and lovastatin (1 mmol/L) + MJ (100 mmol/L) respectively, which means that both mevalonate and non-mevalonate pathway contribute to taxol biosynthesis, and the latter is the main source of IPP. Inhibitors lovastatin and fosmidomycin both promoted the transcriptional expression of hmgr and dxr, which indicated a metabolic cross talk between cytosolic and plastidial pathways of taxol biosynthesis.
Liu
Zhi
Z
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. yulj@hust.edu.cn
Yu
Long-Jiang
LJ
Li
Chun-Yan
CY
Zhao
Chun-Fang
CF
D018929:Cell Culture Techniques; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D015394:Molecular Structure; D017239:Paclitaxel / Q000096:biosynthesis* / Q000737:chemistry; D020946:Taxus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D005578:Fosfomycin; C024640:fosmidomycin; D008148:Lovastatin; D017239:Paclitaxel