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

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. AbbreviationsAACTacetyl-CoACacetyltransferase CMK4-(cytidine5-diphospho)-2-C-methylerythritol kinase CPPcopalyl diphosphate CPScopalyl diphosphate synthase DMAPPdimethylallyl diphosphate DXP1-deoxy-D-xylulose5-phpphate DXR1-deoxy-D-xylulose5-phosphatereductoisomerase DXS1-deoxy-D-xylulose5-phosphatesynthase FPPfarnesyl diphosphate FPPSfarnesyl diphosphatesynthase GGPPgeranylgeranyl diphosphate GGPPSgeranylgeranyldiphosphate synthase GPPgeranyl diphosphate GPPSgeranyl diphosphate synthase HDRhydroxymethylbutenyl 4–diphosphatereductase HDShydroxymethybutenyl-4–diphosphate synthase HMBPP1–hydroxy-2–methyl-2–(E)-buteny4–diphosphate HMGRHMG-CoA reductase HMGS3–hydroxy-3–methylglutaryl-CoA synthase IPPisopentenyldiphosphate KSLkaurenesynthase-like LAAlithospermic acid A LABlithospermic acid B MCTMEP cytidyltransferase MDCmevalonate 5-diphosphate decarboxylase MECPS2-C-methylerythritol-2,4-cyclodiphosphate synthase MEP2-c-methyl-D-erythritd 4-phosphate MKmevalonate kinase PMKphophomevalonate kinase RArosmarinic acid SABsalvianolic acid B TA-Itanshinone I TA-IIAtanshinone IIA