title: Increased accumulation of the cardio-cerebrovascular disease treatment drug tanshinone in Salvia miltiorrhiza hairy roots by the enzymes 3-hydroxy-3-methylglutaryl CoA reductase and 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
abstract: Tanshinone is widely used for treatment of cardio-cerebrovascular diseases with increasing demand. Herein, key enzyme genes SmHMGR (3-hydroxy-3-methylglutaryl CoA reductase) and SmDXR (1-deoxy-D-xylulose 5-phosphate reductoisomerase) involved in the tanshinone biosynthetic pathway were introduced into Salvia miltiorrhiza (Sm) hairy roots to enhance tanshinone production. Over-expression of SmHMGR or SmDXR in hairy root lines can significantly enhance the yield of tanshinone. Transgenic hairy root lines co-expressing HMGR and DXR (HD lines) produced evidently higher levels of total tanshinone (TT) compared with the control and single gene transformed lines. The highest tanshinone production was observed in HD42 with the concentration of 3.25 mg g(-1) DW. Furthermore, the transgenic hairy roots showed higher antioxidant activity than control. In addition, transgenic hairy root harboring HMGR and DXR (HD42) exhibited higher tanshinone content after elicitation by yeast extract and/or Ag(+) than before. Tanshinone can be significantly enhanced to 5.858, 6.716, and 4.426 mg g(-1) DW by YE, Ag(+), and YE-Ag(+) treatment compared with non-induced HD42, respectively. The content of cryptotanshinone and dihydrotanshinone was effectively elevated upon elicitor treatments, whereas there was no obvious promotion effect for the other two compounds tanshinone I and tanshinone IIA. Our results provide a useful strategy to improve tanshinone content as well as other natural active products by combination of genetic engineering with elicitors.
authors.affiliation: Development Center of Plant Germplasm Resources, College of Life and Environment Sciences, Shanghai Normal University, Shanghai, 200234, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Luo
authors.forename: Guanhua
authors.initials: G
authors.lastname: Ju
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Hao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Xiao
authors.forename: Lijie
authors.initials: L
authors.lastname: Cui
authors.forename: Guoyin
authors.initials: G
authors.lastname: Kai
mesh_terms: D045784:Abietanes / Q000096:biosynthesis* / Q000737:chemistry; D019747:Aldose-Ketose Isomerases / Q000096:biosynthesis / Q000235:genetics*; D001713:Biphenyl Compounds / Q000737:chemistry; D002317:Cardiovascular Agents / Q000737:chemistry / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis / Q000235:genetics*; D010084:Oxidation-Reduction; D010851:Picrates / Q000737:chemistry; D010940:Plant Proteins / Q000096:biosynthesis / Q000235:genetics; D018517:Plant Roots / Q000201:enzymology / Q000235:genetics; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000201:enzymology / Q000235:genetics*
chemical_list: D045784:Abietanes; D001713:Biphenyl Compounds; D002317:Cardiovascular Agents; D016166:Free Radical Scavengers; D010851:Picrates; D010940:Plant Proteins; C021751:tanshinone; C004931:1,1-diphenyl-2-picrylhydrazyl; D006903:Hydroxymethylglutaryl CoA Reductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases