Noscapine, a isoquinoline alkaloid first characterized from opium poppy, has a potent anticancer activity thanks to its ability to block cell division by inhibiting tubulin polymerization. However, the biochemical pathway leading to its biosynthesis is unknown.
Thilo Winzer, University of York, UK, and colleagues identified the genes involved in the synthesis of the alkaloid and proposed its biosynthetic pathway. The researches revealed that the first biochemical steps consist of scoulerine conversion into tetrahydrocolumbamine, from which canadine is synthesized. Following methylation, canadine is transformed into secoberbine intermediates subsequently converted into papaveroxine. Removal of an acetyl group from papaveroxine leads to production of narcotinehemiacetal which is finally converted to noscapine by a dehydrogenase/reducatase enzyme.
These findings open the doors to noscapine pharmaceutical production from poppies or other systems.
- A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine,
T. Winzer, V. Gazda, Z. He, F. Kaminski, M. Kern, T. R. Larson, Y. Li, F. Meade, R. Teodor, F. E. Vaistij, C. Walker, T. A. Bowser, I. A Graham,
Science 2012, 336(6089), 1704–1708.
amazing work. It may boost the cancer theraphy.