“…Substrate promiscuity in IDS enzymes has been long established, particularly in FPPSs, which can accept a range of artificial isoprenoids at both allylic and non-allylic binding sites (see Couillaud et al, 2022 for a recent review). Experimental evidence from the microorganism Sulfolobus acidocaldarius GGPPS has found it to be similarly open to atypical substrates, including HIPP (Ohnuma et al, 1998;Nagaki et al, 2004). Lepidoptera have evolved FPPS enzymes that selectively extend homo (ethyl-branched)-DMAPP for juvenile hormone synthesis, which can also act as a non-optimal substrate for spruce budworm GGPPS (Sen et al, 2007;Barbar et al, 2013).…”