Sesame is a major oil seed crop that is used for cooking, candles, cosmetics and many other applications worldwide. In addition, sesame produces a variety of phenylpropanoid-derived specialized metabolites in its seeds, called lignan. The lineage-specific, structural diversity of lignans suggests the functional differentiation of lignan biosynthetic enzymes, however the molecular mechanism(s) underlying diastereomeric specialization remains unknown. Ono et al. (on pp. 2278–2287) report that a methylenedioxy bridge forming P450, CYP81Q3 from wild sesame is associated with the diastereomerically characteristic lignans, 2-episesalatin and alatumin, suggesting that functional differentiation of a P450 contributes to the metabolic diversity of sesame lignans.