Galanthamine production by Leucojum aestivum in vitro shoot cultures

Galanthamine, an Amaryllidaceae alkaloid, become an important therapeutic options used to slow down the process of neurological degeneration in Alzheimer's disease. Although chemical synthesis of galanthamine has been successfully established, the main commercial source in Bulgaria for the production of galanthamine-based medicines (under trade name Nivalin®) is Leucojum aestivum, an Euro-Mediterranean species, also called summer snowflake. Since 1989, prescription regime of the utilization of this plant species has been imposed and, from these perspectives, galanthamine production from in vitro cultures is considered as an alternative.

In vitro callus and shoot cultures of L. aestivum previously obtained were checked for galanthamine production. It was established that the amount of accumulated galanthamine strongly depended on the level of differentiation. The maximum amount of accumulated biomass (15.6g/L), the endo-galanthamine content (55.6µg/g) and the exo-galanthamine yield (1.6mg/L) were achieved after 5 weeks of submerged cultivation of L. aestivum 80 shoot culture, in a modified MS medium, under illumination.

Further the galanthamine bioproduction process was up-scaled in different cultivation systems, such as column bioreactor and RITA® temporary immersion systems. Based on the obtained results, the in vitro shoot cultures of L. aestivum could be considered as an attractive alternative for galanthamine production.

Acknowledgements: This research has been supported by a Marie Curie European Re-Integration Grant under contract number MERG-CT-2007–046427.