Proposed epi-ISY step in antirrhinoside biosynthesis. The biosynthesis of antirrhinoside has been elucidated based on deuterium labeling studies (15–18). Antirrhinoside biosynthesis requires a configuration of the nepetalactol precursor (blue arrow) different from that found previously with CrISY (red arrows). We hypothesize that an epi-ISY performs the synthesis of 7-epi-nepetalactol in A. majus. The CrISY reaction involves hydride transfer from NADPH to generate an enolate intermediate that then cyclizes to various configurational isomers of nepetalactol and iridodial. For the major cis—trans nepetalactol and cis—trans iridodial product of CrISY, the stereochemical nomenclature and atom numbering are shown in purple.