Un articolo appena pubblicato su PNAS illustra i meccanismi di sintesi, secrezione, compartimentazione ed escrezione degli alcaloidi della Vinca (Catharanthus roseus), e descrive gli effetti che questi meccanismi hanno sulla facilità (o meno) di ottenere farmaci per il trattamento dei tumori. Infatti, mentre i farmaci derivano dall’accoppiamento dei due alcaloidi catarantina e vindolina, i percorsi metabolici ed i meccanismi di secrezioni nella pianta risultano in una compartimentazione stretta che impedisce l’accoppiamento delle due molecole nella pianta. Una di esse, la catarantina, che mostra attività antifungina ed insettorepellente, viene secreta infatti nella cera cuticolare della foglia (dove queste attività hanno più senso), mentre la vindolina è presente esclusivamente all’interno delle cellule della foglia.

The monoterpenoid indole alkaloids (MIAs) of Madagascar periwinkle (Catharanthus roseus) continue to be the most important source of natural drugs in chemotherapy treatments for a range of human cancers. These anticancer drugs are derived from the coupling of catharanthine and vindoline to yield powerful dimeric MIAs that prevent cell division. However the precise mechanisms for their assembly within plants remain obscure. Here we report that the complex development-, environment-, organ-, and cell-specific controls involved in expression of MIA pathways are coupled to secretory mechanisms that keep catharanthine and vindoline separated from each other in living plants. Although the entire production of catharanthine and vindoline occurs in young developing leaves, catharanthine accumulates in leaf wax exudates of leaves, whereas vindoline is found within leaf cells. The spatial separation of these two MIAs provides a biological explanation for the low levels of dimeric anticancer drugs found in the plant that result in their high cost of commercial production. The ability of catharanthine to inhibit the growth of fungal zoospores at physiological concentrations found on the leaf surface of Catharanthus leaves, as well as its insect toxicity, provide an additional biological role for its secretion. We anticipate that this discovery will trigger a broad search for plants that secrete alkaloids, the biological mechanisms involved in their secretion to the plant surface, and the ecological roles played by them.