title: Identification of geranylgeranyl diphosphate synthase genes from Tripterygium wilfordii.
abstract: We found triptolide synthesis is correlated with the expressions of TwGGPPS1 and TwGGPPS4 . This lays the foundation for future studies of biosynthetic pathways for triptolide and other diterpenoids in T. wilfordii. Tripterygium wilfordii is a traditional Chinese medical plant commonly used to treat rheumatoid arthritis. One of its main bioactive compounds is triptolide, which is identified as an abietane-type diterpenoid natural product. Geranylgeranyl diphosphate synthase (GGPPS) catalyses the synthesis of GGPP (geranylgeranyl diphosphate), the common precursor of diterpenes, and is therefore a crucial enzyme in diterpene biosynthesis. A previous study showed that GGPP could be catalyzed by copalyl diphosphate synthase and kaurene synthase like of Salvia miltiorrhiza (SmCPS, SmKSL) to miltiradiene, a key intermediate in tanshinone biosynthesis. In this paper, five new full-length cDNAs (TwGGPPS) encoding GGPP synthases were cloned from T. wilfordii. Sequence comparisons revealed that all six TwGGPPSs (including TwGGPPS2 cloned previously) exhibit similarities to GGPPSs of other plants. Subsequent functional complement assays demonstrated that TwGGPPS1, TwGGPPS4 and TwGGPPS5 can participate in miltiradiene biosynthesis in the recombinant E. coli. Correlation analysis of gene expressions and secondary metabolite accumulation indicated that TwGGPPS1 and TwGGPPS4 are likely involved in the biosynthesis of triptolide. These findings lay the foundation for future studies of the biosynthetic pathways for triptolide and other diterpenoids in T. wilfordii.
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China. zhangmeng8846@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.|National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Su
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 41296, Göteborg, Sweden.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Zhou
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China. wxj0517@sina.com.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.|National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Yu-Ru
authors.initials: YR
authors.lastname: Tong
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Hu
authors.affiliation: National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. huangluqi01@126.com.
authors.forename: Lu-Qi
authors.initials: LQ
authors.lastname: Huang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China. weigao@ccmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D000085:Acetates / Q000378:metabolism; D000595:Amino Acid Sequence; D053898:Biosynthetic Pathways; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D051231:Farnesyltranstransferase / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D054883:Oxylipins / Q000378:metabolism; D010616:Phenanthrenes / Q000737:chemistry / Q000378:metabolism*; D010802:Phylogeny; D010937:Plant Growth Regulators / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D029757:Tripterygium / Q000201:enzymology* / Q000235:genetics
chemical_list: D000085:Acetates; D003517:Cyclopentanes; D004224:Diterpenes; D004852:Epoxy Compounds; D054883:Oxylipins; D010616:Phenanthrenes; D010937:Plant Growth Regulators; D010940:Plant Proteins; D011106:Polyisoprenyl Phosphates; C573600:miltiradiene; C001899:triptolide; C072239:methyl jasmonate; D051231:Farnesyltranstransferase; C002963:geranylgeranyl pyrophosphate
keywords: Biosynthesis; GGPPS; Tripterygium wilfordii; Triptolide