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. AbbreviationsAACT acetyl-CoACacetyltransferaseCMK 4-(cytidine5-diphospho)-2-C-methylerythritol kinaseCPP copalyl diphosphateCPS copalyl diphosphate synthaseDMAPP dimethylallyl diphosphateDXP 1-deoxy-D-xylulose5-phpphateDXR 1-deoxy-D-xylulose5-phosphatereductoisomeraseDXS 1-deoxy-D-xylulose5-phosphatesynthaseFPP farnesyl diphosphateFPPS farnesyl diphosphatesynthaseGGPP geranylgeranyl diphosphateGGPPS geranylgeranyldiphosphate synthaseGPP geranyl diphosphateGPPS geranyl diphosphate synthaseHDR hydroxymethylbutenyl 4–diphosphatereductaseHDS hydroxymethybutenyl-4–diphosphate synthaseHMBPP 1–hydroxy-2–methyl-2–(E)-buteny4–diphosphateHMGR HMG-CoA reductaseHMGS 3–hydroxy-3–methylglutaryl-CoA synthaseIPP isopentenyldiphosphateKSL kaurenesynthase-likeLAA lithospermic acid ALAB lithospermic acid BMCT MEP cytidyltransferaseMDC mevalonate 5-diphosphate decarboxylaseMECPS 2-C-methylerythritol-2,4-cyclodiphosphate synthaseMEP 2-c-methyl-D-erythritd 4-phosphateMK mevalonate kinasePMK phophomevalonate kinaseRA rosmarinic acidSAB salvianolic acid BTA-I tanshinone ITA-IIA tanshinone IIA.