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.AbbreviationsAACTacetyl-CoACacetyltransferaseCMK4-(cytidine5-diphospho)-2-C-methylerythritol kinaseCPPcopalyl diphosphateCPScopalyl diphosphate synthaseDMAPPdimethylallyl diphosphateDXP1-deoxy-D-xylulose5-phpphateDXR1-deoxy-D-xylulose5-phosphatereductoisomeraseDXS1-deoxy-D-xylulose5-phosphatesynthaseFPPfarnesyl diphosphateFPPSfarnesyl diphosphatesynthaseGGPPgeranylgeranyl diphosphateGGPPSgeranylgeranyldiphosphate synthaseGPPgeranyl diphosphateGPPSgeranyl diphosphate synthaseHDRhydroxymethylbutenyl 4–diphosphatereductaseHDShydroxymethybutenyl-4–diphosphate synthaseHMBPP1–hydroxy-2–methyl-2–(E)-buteny4–diphosphateHMGRHMG-CoA reductaseHMGS3–hydroxy-3–methylglutaryl-CoA synthaseIPPisopentenyldiphosphateKSLkaurenesynthase-likeLAAlithospermic acid ALABlithospermic acid BMCTMEP cytidyltransferaseMDCmevalonate 5-diphosphate decarboxylaseMECPS2-C-methylerythritol-2,4-cyclodiphosphate synthaseMEP2-c-methyl-D-erythritd 4-phosphateMKmevalonate kinasePMKphophomevalonate kinaseRArosmarinic acidSABsalvianolic acid BTA-Itanshinone ITA-IIAtanshinone IIA