Manipulation of ginsenoside heterogeneity of Panax notoginseng cells in flask and bioreactor cultivations with addition of phenobarbital.
Structure-similar ginsenosides have different or even totally opposite biological activities, and manipulation of ginsenoside heterogeneity is interesting and significant to biotechnological application. In this work, addition of 1 mM phenobarbital to cell cultures of Panax notoginseng at a relatively high inoculation size of 7.6 g dry cell weight (DW)/L enhanced the production of protopanaxatriol-type (Rg(1) + Re) ginsenosides in both shake flask and airlift bioreactor (ALR, 1 L working volume). The content of Rg(1) + Re in the ALR was increased from 42.5 +/- 4.0 mg per gram DW in untreated cell cultures (control) to 56.4 +/- 4.6 mg per gram DW with addition of 1.0 mM phenobarbital. The maximum productivity of Rg(1) + Re in the ALR reached 5.66 +/- 0.38 mg L(-1) d(-1), which was almost 3.3-fold that of control. The maximum ratio of the detectable ginsenosides protopanaxatriol:protopanaxadiol (Rb(1)) was 7.6, which was about twofold that of control. The response of protopanaxadiol 6-hydroxylase (P6H) activity to phenobarbital addition coincided with the above-mentioned change of ginsenoside heterogeneity (distribution). Phenobarbital addition is considered as a useful strategy for manipulating the ginsenoside heterogeneity in bioreactor with enhanced biosynthesis of protopanaxatriol by P. notoginseng cells.
Yue
Cai-Jun
CJ
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. jjzhong@sjtu.edu.cn
Zhong
Jian-Jiang
JJ
D019149:Bioreactors / Q000382:microbiology*; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000378:metabolism*; D053723:Panax notoginseng / Q000187:drug effects* / Q000378:metabolism*; D010634:Phenobarbital / Q000008:administration & dosage*; D010865:Pilot Projects
D036145:Ginsenosides; D010634:Phenobarbital