Tabersonine is a terpene indole alkaloid found in the medicinal plant Catharanthus roseus. Tabersonine is hydroxylated at the 16 position by the enzyme tabersonine 16-hydroxylase (T16H) to form 16-hydroxytabersonine. The enzyme leading to its formation is currently unknown. Tabersonine is the first intermediate leading to the formation of vindoline one of the two precursors required for vinblastine biosynthesis. Bioinformatics and virus-induced gene silencing (VIGS)-guided gene discovery combined with biochemical enzyme assays show that tabersonine 3-oxygenase (T3O) and tabersonine 3-reductase (T3R) are required to form 3-hydroxy-16-methoxy-2,3-dihydrotabersonine, an intermediate in the formation of anticancer drug precursor vindoline from tabersonine. In the absence of T3R, tabersonine is converted by T3O to a series of byproducts that can no longer be used by T3R, suggesting a concerted reaction mechanism.
-P984.gif)