Fig. 1
Diterpene biosynthetic pathways from the universal precursor geranylgeranyl diphosphate (GGPP) towards forskolin and ferruginol, compounds present in the root cork cells of Coleus forskohlii. The common diterpene precursor GGPP is formed by four C5 units from the plastid based 2-C-methyl-d-erythritol 4-phosphate pathway (MEP). GGPP is cyclized by the class II diterpene synthase (diTPS), CfTPS1, to (+)-copalyl-diphosphate and further to miltiradiene by class I diTPS, CfTPS3. Miltiradiene can undergo non-enzymatic oxidation into abietatriene, which is hydroxylated to ferruginol by CYP76AH15. The forskolin precursor 13R-manoyl oxide is formed from GGPP through (+)-8-hydroxy-copalyl diphosphate by the class II diTPS, CfTPS2, and further to 13R-manoyl oxide by the class I diTPS, CfTPS3. 13R-manoyl oxide is further converted by CYP76AH15 to 11-oxo-13R-manoyl oxide, which is further converted to 9-deoxy-7-deacetylforskolin by the multifunctional CYP76AH11 and to deacetyl-forskolin by CYP76AH16. Finally, deacetyl-forskolin is acetylated at carbon 7 by CfACT1-8 to forskolin