Epi-iridoids are pervasive in the Plantaginaceae as well as numerous other plant families (such as Lamiaceae (29), Rubiaceae (30), Orobanchaceae (31), and Paulowniaceae (29)). With several hundred epi-iridoid–derived structures reported, AmISY may become a reference point for the identification of epi-ISY enzymes in these pathways. We predict that these epi-synthases can be identified by inspection of the distinct active site residues (Trp-149, Trp-246, Leu-342, Val-345, and Val-346) identified by the AmISY homology model and by mutation.