Isolated from the plants Rosmarinus officinalis (rosemary) and Salvia miltiorrhiza. The enzyme from the plant Selaginella moellendorffii is mutifunctional and also catalyses EC 5.5.1.12, copalyl diphosphate synthase [2].
Nicotiana benthamiana transient expression of copalyl diphosphate synthase CPS1 with isoform KSL1 results in the production of miltiradiene plus about 25% abietatriene; Nicotiana benthamiana transient expression of copalyl diphosphate synthase CPS1 with isoform KSL1 results in the production of miltiradiene plus about 25% abietatriene
MDS is a bifunctional miltiradiene synthase catalyzing the cyclization reaction of geranylgeranyl diphosphate via (+)-copalyl diphosphate to afford miltiradiene as a final product
elevated expression in trichome of young leaf. Isoform KSL1 transcript level is less than 1% of expression of isoform KSL2; elevated expression in trichome of young leaf. Isoform KSL1 transcript level is less than 1% of expression of isoform KSL2
expression of copalyl diphosphate synthase and miltiradiene synthase in Saccharomyces cerevisiae, results in production of 4.2 mg/l miltiradiene. Miltiradiene production increases to 8.8 mg/l by improving supply of geranylgeranyl diphosphate by over-expression of a fusion gene of farnesyl diphosphate synthase ERG20 and endogenous geranylgeranyl diphosphate synthase BTS1 together with a heterologous geranylgeranyl diphosphate synthase from Sulfolobus acidocaldarius. Combinatorial overexpression of truncated 3-hydroxyl-3-methylglutaryl-CoA reductase with a mutated global regulatory factor upc2.1 and ERG20-BTS1-geranylgeranyl diphosphate synthase genes has synergetic effects on miltiradiene production, increasing titer to 61.8 mg/l. In fed-batch fermentation 488 mg/l miltiradiene can be produced