Proposed biosynthetic pathway of sclareol and related diterpenes in Salvia sclarea. The suggested biosynthetic pathway of sclareol 4 as the predominant diterpene in S. sclarea and other minor constituents detected in planta, such as manool 6 as well as manoyl oxide 7 and 13-epi-manoyl oxide 8, requires the activity of at least two monofunctional diTPSs. A class II enzyme catalyzes the protonation-initiated cyclization of (E,E,E)-geranylgeranyl diphosphate (GGPP) 1 to form labda-13-en-8- ol diphosphate (LPP)3 or (9 S,10 S)-copalyl diphosphate (CPP) 5 (i.e., CPP of normal or (+)-stereochemistry) via a labda-13-en-8-yl diphosphate 2 carbocation. Catalyzed by class I diTPS activity, ionization of the diphosphate ester of LPP 3 or CPP 5 results in the formation of sclareol 4 and manool 6, respectively. In addition, manoyl oxide 7 and 13-epi-manoyl oxide 8 may occur as a product of this biosynthetic pathway.