The metabolic role of AmISY in the plant is supported by the high expression levels in leaves, the physiologically relevant catalytic parameters, and the R selectivity that is consistent with earlier feeding experiments. Moreover, no other iridoid synthase homologs from A. majus were highly active in vitro. However, if we make the reasonable assumption that AmISY is the metabolically relevant enzyme, then the mechanism by which the diverse AmISY products are channeled into the pathway of the abundant natural product antirrhinoside remains an unsolved problem. Biosynthesis of antirrhinoside requires the C7-R stereochemistry, which is indeed produced by AmISY. However, antirrhinoside also requires the cis—cis diastereomer. In contrast, the major product of AmISY is C7-R-cis-trans, whereas C7-R-cis-cis makes up only a few percent of the product.