Metabolic engineering tanshinone biosynthetic pathway in Salvia miltiorrhiza hairy root cultures

Guoyin Kai*, Hui Xu, Congcong Zhou, Pan Liao, Jianbo Xiao, Xiuqin Luo, Lijia You, Lin Zhang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

192 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)319-327
Number of pages9
JournalMetabolic Engineering
Volume13
Issue number3
Early online date16 Feb 2011
DOIs
Publication statusPublished - May 2011

Scopus Subject Areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

User-Defined Keywords

  • Diterpenoid
  • Metabolic engineering
  • Salvia miltiorrhiza bunge
  • Tanshinone
  • Transformation

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