Biosynthesis of bioactive ingredients of Salvia miltiorrhiza and advanced biotechnologies for their production

Abstract

This review deals with the progress in the biosynthesis and regulation of tanshinones and salvianolic acids as well as the prospects and challenges for producing such compounds through biotechnology techniques. Tanshinones (lipophilic diterpenoids) and salvianolic acids (hydrophilic phenolic acids) are valuable natural products from danshen (Salvia miltiorrhiza Bunge) with remarkable clinical efficacy to treat cardiovascular diseases, with potential application in the treatment of cancer and possibly other disorders. The significant bioactivities of S. miltiorrhiza inspired scientists to explore its biosynthetic mechanism that promotes the production of these compounds. Computational and comparative genomics and transcriptomics have been used to analyse a number of pathway genes, transcription factors and microRNAs that are associated with the biosynthesis and regulation of tanshinones and salvianolic acids. At the same time, plant cell and tissue culture, transgenic plants, microbial biotransformation and metabolic engineering have been used to synthesise all these compounds.

Chromosome Doubling-Enhanced Biomass and Dihydrotanshinone I Production in Salvia miltiorrhiza, A Traditional Chinese Medicinal Plant

“…The other compound, SA-B, was also found in the root and the potent therapeutic effects which are mainly for cardiovascular diseases [4]. It has been reported that tanshinones are synthesized via the terpenoid pathway, whereas salvianolic acids through the phenylpropanoid pathway [24]. In this study, the root extract of 4 x plants accumulated significantly higher concentration of DT-I than 2 x plants.…”

Effect the accumulation of bioactive constituents of a medicinal plant (Salvia Miltiorrhiza Bge.) by arbuscular mycorrhizal fungi community

“…Salvia miltiorrhiza Bunge (Lamiaceae, Salvia), also known as Danshen, has demonstrated notable antioxidant, antibacterial, anticoagulant, and anti-tumor activities and has been commonly used to treat cardiovascular diseases for almost 2,000 years [ 15 – 17 ]. As a mycorrhizal-dependent medicinal plant, S. miltiorrhiza can form a good symbiosis with various AMFs [ 18 – 20 ].…”

De novo Biosynthesis of Salvianolic Acid B in Saccharomyces cerevisiae Engineered with the Rosmarinic Acid Biosynthetic Pathway

“…19−21 Phenylalanine ammonia-lyase (PAL), cinnamic acid 4-hydroxylase (C4H), 4-hydroxycinnamic acid CoA-ligase (4CL), tyrosine aminotransferase (TAT), hydroxyphenylpyruvate reductase (HPPR), rosmarinic acid synthase (RAS), and cytochrome P450-dependent monooxygenase (CYP98A14) were involved in RA biosynthesis. 19,20,22 However, the direct evidence for the formation of SAB from RA is still absent in the literature. natural products and serves as an alternative to extraction from plant biomass.…”

“…From the view of the chemical structure, SAB can be seen as the condensation product of two molecules of caffeic acid (CA) and two molecules of 3,4-dihydroxyphenyllactic acid (DHPL, also named danshensu or salvianic acid A) or the coupling product of two RA phenoxyl radicals (Figure ), and laccase was assumed to be responsible for the formation of SAB from RA in S. miltiorrhiza. , In plants, RA is proposed to be synthesized through the condensation of 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid, followed by 3- and 3′-hydroxylation, or the coupling of 4-coumaroyl-CoA and DHPL, followed by 3-hydroxylation, starting from phenylalanine and tyrosine. − Phenylalanine ammonia-lyase (PAL), cinnamic acid 4-hydroxylase (C4H), 4-hydroxycinnamic acid CoA-ligase (4CL), tyrosine aminotransferase (TAT), hydroxyphenylpyruvate reductase (HPPR), rosmarinic acid synthase (RAS), and cytochrome P450-dependent monooxygenase (CYP98A14) were involved in RA biosynthesis. ,, However, the direct evidence for the formation of SAB from RA is still absent in the literature.…”