title: Metabolic engineering tanshinone biosynthetic pathway in Salvia miltiorrhiza hairy root cultures.
abstract: Tanshinone is a group of active diterpenes widely used in treatment of cardiovascular diseases. Here, we report the introduction of genes encoding 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), 1-deoxy-D-xylulose-5-phosphate synthase (DXS) and geranylgeranyl diphosphate synthase (GGPPS) involved in tanshinone biosynthesis into Salvia miltiorrhiza hairy roots by Agrobacterium-mediated gene transfer technology. Overexpression of SmGGPPS and/or SmHMGR as well as SmDXS in transgenic hairy root lines can significantly enhance the production of tanshinone to levels higher than that of the control (P<0.05). SmDXS showed much more powerful pushing effect than SmHMGR in tanshinone production, while SmGGPPS plays a more important role in stimulating tanshinone accumulation than the upstream enzyme SmHMGR or SmDXS in S. miltiorrhiza. Co-expression of SmHMGR and SmGGPPS resulted in highest production of tanshinone (about 2.727 mg/g dw) in line HG9, which was about 4.74-fold higher than that of the control (0.475 mg/g dw). All the tested transgenic hairy root lines showed higher antioxidant activity than the control. To our knowledge, this is the first report on enhancement of tanshinone content and antioxidant activity achieved through metabolic engineering of hairy roots by push-pull strategy in S. miltiorrhiza.
authors.affiliation: Laboratory of Plant Biotechnology, College of Life and Environment Sciences, Shanghai Normal University, Shanghai, PR China. gykai@shnu.edu.cn
authors.forename: Guoyin
authors.initials: G
authors.lastname: Kai
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Congcong
authors.initials: C
authors.lastname: Zhou
authors.forename: Pan
authors.initials: P
authors.lastname: Liao
authors.forename: Jianbo
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Luo
authors.forename: Lijia
authors.initials: L
authors.lastname: You
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000096:biosynthesis*; D005818:Genetic Engineering; D008025:Ligases / Q000096:biosynthesis* / Q000235:genetics; D010940:Plant Proteins / Q000096:biosynthesis* / Q000235:genetics; D018517:Plant Roots / Q000201:enzymology*; D030821:Plants, Genetically Modified / Q000201:enzymology* / Q000235:genetics; D027561:Salvia miltiorrhiza / Q000201:enzymology* / Q000235:genetics
chemical_list: D045784:Abietanes; D010940:Plant Proteins; C021751:tanshinone; D008025:Ligases