title: A systematic approach to expound the variations in taxane production under different dissolved oxygen conditions in Taxus chinensis cells.
abstract: Our results provide an evidence that the changes in taxane production caused by dissolved oxygen shifts could be associated with the global variations in the cell central carbon metabolism. Taxol is an important taxane synthesized by the Taxus plant. A two-stage culture of Taxus in vitro has been considered as an attractive alternative approach to produce Taxol and its precursors. To investigate the consequences of dissolved oxygen (DO) shifts for cell primary and secondary metabolism, we conducted metabolomic and transcriptomic profiling analyses under low dissolved oxygen (LDO), medium dissolved oxygen (MDO), and high dissolved oxygen (HDO) conditions in a suspension culture of Taxus chinensis cells. Under LDO, the results indicate a significant increase in the production of Taxol and its main precursors by 3.4- to 1.4-fold compared with those under MDO and HDO on 9th day. Multiple acyl taxanes (MAT) are abundant taxanes in the cells, and exhibited only a slight increase under the same conditions. Metabolomic analysis based on 209 primary metabolites indicated that several pathways in central carbon metabolism were involved, including the enhancement of the glycolysis pathway of glucose-6-phosphate to fructose-6-phosphate and pyruvate and the mevalonate pathway of terpene biosynthesis, and decline in the tricarboxylic acid pathway under LDO. These results indicate the mechanism by which related taxanes accumulate through enhancing the supplies of substrates and expression levels of hydroxylases. Excess acetyl-CoA supply induced by high oxygen stress was found to be correlated with high productivity of MAT. Our results provide an evidence that the changes in taxane production caused by DO shifts could be associated with the global variations in the cell central carbon metabolism.
authors.affiliation: Department of Biotechnology, Institute of Resource Biology and Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. cfzhao@hust.edu.cn.|Key Laboratory of Molecular Biophysics Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. cfzhao@hust.edu.cn.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Biotechnology, Institute of Resource Biology and Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. songguanghao888888@163.com.|Key Laboratory of Molecular Biophysics Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. songguanghao888888@163.com.
authors.forename: Guanghao
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Biotechnology, Institute of Resource Biology and Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.|Key Laboratory of Molecular Biophysics Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Biotechnology, Institute of Resource Biology and Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.|Key Laboratory of Molecular Biophysics Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors.forename: Yanshan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Biotechnology, Institute of Resource Biology and Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.|Key Laboratory of Molecular Biophysics Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Biotechnology, Institute of Resource Biology and Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.|Key Laboratory of Molecular Biophysics Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Institute of Resource Biology and Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. yulongjiang@hust.edu.cn.|Key Laboratory of Molecular Biophysics Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. yulongjiang@hust.edu.cn.
authors.forename: Long Jiang
authors.initials: LJ
authors.lastname: Yu
mesh_terms: D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D018506:Gene Expression Regulation, Plant; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055442:Metabolome / Q000235:genetics; D055432:Metabolomics / Q000379:methods; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D043823:Taxoids / Q000378:metabolism*; D020946:Taxus / Q000166:cytology* / Q000235:genetics / Q000378:metabolism
chemical_list: D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D002244:Carbon; D010100:Oxygen
keywords: Central carbon metabolism; Dissolved oxygen; Hydroxylase; Metabolomics; Taxane profiling; Taxus chinensis