Meleagrin is a roquefortine C-derived bioactive benzylisoquinoline alkaloid. Meleagrin and the other intermediates in this pathway are derived from deep ocean sediment-derived Penicillium species. It has other derivatives as well, oxaline for example. It is important in treating c-Met-dependent metastatic and invasive breast malignancies because of its top c-Met inhibitory action and antimicrobial as well as anti-proliferate abilities. This pathway is part of a larger pathway stemming from the compound tryptophan and shows the biosynthesis of meleagrin using a series of enzymes. The intermediate at which the pathway branches is roquefortine C. From the intermediate histidyltryptophyldiketopiperazine, the pathway illustrates two ways in which the pathways branching intermediate roquefortine C is synthesized. Both these ways each use the enzymes cytochrome P450 monooxygenase roqR and roquefortine prenyltransferase roqD in reversed order and via two different intermediates. The branching of the pathway from roquefortine C leads to either N1-hydroxy-roquefortine C or glandicoline A where glandicoline A is the direct way and N1-hydroxy-roquefortine C or glandicoline A acts as an intermediate route, both leading to the intermediate glandicoline B. This way shows that glandicoline A is not needed for the synthesis of glandicoline B and uses a novel intermediate roquefortine L. However, in both ways, the enzyme cytochrome P450 monooxygenase roqO has been used exculsively for glandicoline B synthesis. N1-hydroxy-roquefortine C also leads to the neoxaline biosynthesis - a compound belonging to the Aspergillaceae family and is known for its weak inhibitory activity of blood platelet aggregation induced by stimulation of the central nervous system of mice. Coming back to the main product of this pathway, glandicoline B goes on to synthesize meleagrin via the enzyme glandicoline B O-methyltransferase roqN.

Meleagrin Biosynthesis References