(a) A sequence similarity network (SSN) of 45 putative class II STCs, including the 12-selected STCs (colored blue) with DxDD motifs, displayed at an e-value cutoff at 10−115. SsDMS and ScDMS are shown in dark blue and light purple, respectively. (b) Biosynthetic gene clusters show that both putative STCs, SsDMS and ScDMS, are located immediately downstream of a Nudix hydrolase. (c) Farnesyl diphosphate (FPP) is cyclized into drimenyl diphosphate (DPP) by SsDMS and ScDMS, and then is hydrolyzed into drimenol by unknown endogenous hydrolases in E. coli. (d) The in vivo experiments showed that both strains of DL10008 and DL10009, containing SsDMS and ScDMS, respectively, were able to produce drimenol; the in vitro enzymatic activity reconstitution indicated that SsDMS is a class II STC forming DPP. DL10007 is a control strain without SsDMS or ScDMS. Std, standard. FOH, an authentic sample of farnesol.