Regulation and metabolic engineering of tanshinone biosynthesis

Salvia miltiorrhiza (Chinese name: danshen) is used in traditional Chinese medicine for the treatment of cardiovascular and cerebrovascular diseases. The tanshinones represent the most important biological active class of compounds present in danshen extracts. They are synthesized via either the cytoplasmic mevalonate or the plastidial 2-C-methyl-D-erythritol-4-phosphate pathway. Here, we summarize recent discoveries regarding the mechanisms underlying tanshinone biosynthesis and how the process is regulated. Tanshinone accumulation in planta is affected by a range of elicitors and by the composition of the culture medium. Its production in hairy root cultures can be enhanced by the over-expression of genes encoding 1-deoxy-D-xylulose 5-phosphate synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, geranylgeranyl diphosphate synthase and allene oxide cyclase. The pathway leading to the biosynthesis of the tanshinone precursors miltiradiene and ferruginol, has been engineered in yeast.