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Manipulation of ginsenoside heterogeneity of Panax notoginseng cells in flask and bioreactor cultivations with addition of phenobarbital.Yue CJ, Zhong JJ State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. jjzhong@sjtu.edu.cn 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. Published 18 January 2008 in Bioprocess Biosyst Eng, 31(2): 95-100.
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