Sesame (Sesamum indicum) is a major oil crop rich in (+)-sesamin, (+)-sesamolin, (+)-sesaminol and other lignans that are phenylpropanoid-derived specialized metabolites. Despite the value of lignans for their health-promoting properties, the biosynthesis of (+)-sesamolin and (+)-sesaminol remained elusive. A genome-based genetic approach identified that the deletion of four C-terminal amino acids (Del4C) in a P450 enzyme CYP92B14 resulted in low (+)-sesamolin content in sesame seeds. Enzyme assays confirmed that recombinant CYP92B14, but not Del4C, biosynthesized (+)-sesamolin from (+)-sesamin through oxidative rearrangement of α-oxy-substituted aryl groups. Unexpectedly, CYP92B14 also converted (+)-sesamin to (+)-sesaminol in vitro. Furthermore, conversion of (+)-sesamin into (+)-sesaminol and (+)-sesamolin by CYP92B14 was enhanced when co-expressed with sesamin synthase CYP81Q1, implying functional coordination of CYP81Q1 with CYP92B14. The discovery of CYP92B14 not only uncovers the last steps in sesame lignan biosynthesis but highlights the remarkable catalytic plasticity of P450s that contributes to metabolic diversity in nature.
