Abstract
Secondary metabolites from plants play key roles in human medicine and chemical industries. Due to limited accumulation of secondary metabolites in plants and their important roles, characterization of key enzymes involved in biosynthetic pathway will enable metabolic engineering or synthetic biology to improve or produce the compounds in plants or microorganisms, which provides an alternative for production of these valuable compounds. Salvia miltiorrhiza, containing tanshinones and phenolic acids as its active compounds, has been widely used for the treatment of cardiovascular and cerebrovascular diseases. The biosynthetic analysis of secondary metabolites in S. miltiorrhiza has made great progress due to the successful genetic transformation system, simplified hairy roots system, and high-throughput sequencing. The cloned genes in S. miltiorrhiza had provided references for functional characterization of the post-modification steps involved in biosynthesis of tanshinones and phenolic acids, and further utilization of these steps in metabolic engineering. The strategies used in these studies could provide solid foundation for elucidation of biosynthetic pathways of diterpenoids and phenolic acids in other species. The present review systematically summarizes recent advances in biosynthetic pathway analysis of tanshinones and phenolic acids as well as synthetic biology and metabolic engineering applications of the rate-limiting genes involved in the secondary metabolism in S. miltiorrhiza.
Highlights
Plant secondary metabolites including terpenes, phenolic compounds, and nitrogen-containing compounds, which are served as signaling or defense molecules, are important to plant development and adaptation, and have significant economic value as resources in human medicine and chemical industries
Though the downstream biosynthetic pathway analysis of tanshinones and phenolic acids is still ongoing, it has made great progress in elucidating the biosynthesis of these secondary metabolites which could provide a solid foundation for other compounds
We systematically reviewed the recent progresses in biosynthetic pathway analysis of tanshinones and phenolic acids as well as synthetic biology and metabolic engineering applications of the rate-limiting genes involved in the secondary metabolism in S. miltiorrhiza from year 2005 to year 2015, and further discussed the analysis and utilization of the metabolic pathways
Summary
Plant secondary metabolites including terpenes, phenolic compounds, and nitrogen-containing compounds, which are served as signaling or defense molecules, are important to plant development and adaptation, and have significant economic value as resources in human medicine and chemical industries. Though the downstream biosynthetic pathway analysis of tanshinones and phenolic acids is still ongoing, it has made great progress in elucidating the biosynthesis of these secondary metabolites which could provide a solid foundation for other compounds. The first cDNA microarray analysis for different stages of S. miltiorrhiza hairy root cultures revealed 203 differentially expressed genes from 4354 cDNA clones, including seven genes (especially two important terpenoid synthases) involved in tanshinone biosynthesis [22]. Combining this transcriptome data with qRT-PCR to analyze these genes expression pattern, 15 CYPs, one 2-oxo-glutarate dependent di-oxygenase (2ODD) and five short-chain alcohol dehydrogenases (SDRs) which co-expressed with SmCPS1, SmKSL1, and CYP76AH1 were predicted to play roles in tanshinones biosynthesis [29] These databases provide valuable resource and full-length candidate genes for further investigation of secondary metabolites biosynthesis in. MJ, ABA, SA, UV-B, GA, ethylene, Ag+, YE stem root root stem stem stem stem root
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