Stress-induced modification of indole alkaloids:Phytomodificines as a new category of specialized metabolites.

This study focuses on the elucidation of the stress-induced reverse changes of major indole alkaloids in Vinca minor, primarily on the postulated conversion of vincamine and vincadifformine to yield 9-methoxyvincamine, minovincine, and minovincinine, respectively. By applying the P450 enzyme inhibitors, naproxen and resveratrol, it was shown that the oxidative reaction involved in the postulated conversion of vincamine and vincadifformine is catalyzed by cytochrome P450 enzymes. In combination with the identification of 9-hydroxyvincamine as a postulated intermediate, this result confirms that the observed stress-induced reverse changes in the alkaloid pattern are caused by modifications of the alkaloids which regularly accumulate in the healthy Vinca minor plants. Up to now, just two main types of defense compounds are distinguished: phytoalexins, which are synthesized de novo from primary metabolites and phytoanticipins, which are constitutively present in plants - either intrinsically active or are activated after cell death by hydrolysis or oxidation of the precursors. In contrast, the results presented in this paper demonstrate that indole alkaloids, representing typical phytoanticipins, are just slightly modified in response to a stress-related elicitation. Accordingly, these modified alkaloids neither represent classical phytoalexins (being synthesized de novo), nor can they be classified as phytoanticipins, since modification does not occur postmortem. Consequently, we propose a new category for these modified alkaloids that we call phytomodificines.