Galanthamine production by Leucojum aestivumL. shoot culture in a modified bubble column bioreactor with internal sections

Abstract

Shoot culture of summer snowflake (Leucojum aestivum L.) was successfully cultivated in an advanced modified glass‐column bioreactor with internal sections for production of Amaryllidaceae alkaloids. The highest amounts of dry biomass (20.8 g/L) and galanthamine (1.7 mg/L) were achieved when shoots were cultured at 22°C and 18 L/(L·h) flow rate of inlet air. At these conditions, the L. aestivum shoot culture possessed mixotrophic‐type nutrition, synthesizing the highest amounts of chlorophyll (0.24 mg/g DW (dry weight) chlorophyll A and 0.13 mg/g DW chlorophyll B). The alkaloids extract of shoot biomass showed high acetylcholinesterase inhibitory activity (IC50 = 4.6 mg). The gas chromatography–mass spectrometry (GC/MS) profiling of biosynthesized alkaloids revealed that galanthamine and related compounds were presented in higher extracellular proportions while lycorine and hemanthamine‐type compounds had higher intracellular proportions. The developed modified bubble‐column bioreactor with internal sections provided conditions ensuring the growth and galanthamine production by L. aestivum shoot culture.

Suitability of bench scale bioreactor system for shoot biomass production and bacoside biosynthesis from Bacopa monnieri (L.)

“…Our results are in line with earlier investigations where nutrients in bioreactor culture medium were not fully depleted [30]. Decrease in the sugar and nitrogen content in modified glass-column bioreactor medium used for cultivation of Leucojum aestivum shoot culture and galanthamine production has also been reported [24]. Decrease in the sugar and nitrogen content in modified glass-column bioreactor medium used for cultivation of Leucojum aestivum shoot culture and galanthamine production has also been reported [24].…”

Bioreactor shoot cultures of Rhododendron tomentosum (Ledum palustre) for a large-scale production of bioactive volatile compounds

“…It indicates that R. tomentosum has great potential to be used in large-scale installations for production of terpenoid compounds. There are few reports which refer to successful accumulation of secondary metabolites in shoot cultures cultivated in various types of bioreactors: dibenzocyclooctadiene lignans (Szopa et al 2017), cardiotonic glycosides (Perez-Alonso et al 2009), flavonoids (wogonin, baicalein, baicalin) (Zobayed et al 2004), polyphenols (Jain et al 2012), xanthones and benzophenone derivatives (Kokotkiewicz et al 2015), indole alkaloids (vindoline, catharanthine) (Yingjin and Zongding 1994), isoquinoline alkaloids (galanthamine) (Georgiev et al 2012), artemisinin (Liu et al 2003), phenolics and flavonoids (Jang et al 2016). However, only few semi-technical sources of volatile oils based on bioreactor-grown microshoots have so far been reported.…”

Towards a Molecular Understanding of the Biosynthesis of Amaryllidaceae Alkaloids in Support of Their Expanding Medical Use

“…Amaryllidaceae alkaloid production based on in vitro grown plant material is being investigated and improved upon, but is to our knowledge not exploited commercially and still considered not economically viable [153,154]. The production of pharmaceutical compounds in heterologous expression systems is much advocated in general, but this may not be the most pragmatic approach for the commercial production of Amaryllidaceae alkaloids.…”