Scale-Up of Centrifugal Impeller Bioreactor for Hyperproduction of Ginseng Saponin and Polysaccharide by High-Density Cultivation of Panax notoginseng Cells

Scale-up of a novel centrifugal impeller bioreactor (CIB) was demonstrated for production of valuable plant-specific secondary metabolites by high-density cell cultures. Initial kLa was identified to be a key factor affecting cell growth and production of ginseng saponin and polysaccharide by high-density cultivation of Panax notoginseng cells in a 3-L CIB. A high level of ginseng saponin and polysaccharide production was obtained at an initial kLa value of 30.2 h^-1. A maximum dry cell weight (DW) and production titer of ginseng saponin and polysaccharide reached 22.0 (plus-minus) 0.3, 1.5 (plus-minus) 0.1, and 2.7 (plus-minus) 0.2 g/L on day 15 with their corresponding productivity of 1140 (plus-minus) 42, 81 (plus-minus) 8, and 150 (plus-minus) 17 mg/(L·d), respectively. Based on initial kLa level, the CIB high-cell-density cultivation process was successfully scaled up from 3 L to 30 L. A maximum DW and production titer of ginseng saponin and polysaccharide in a 30-L CIB reached 25.5 (plus-minus) 0.5, 1.7 (plus-minus) 0.1, and 2.9 (plus -minus) 0.1 g/L (on day 15) at an initial kLa value of 28.7 h^-1, respectively, and their corresponding productivity was 1340 (plusminus) 56, 91 (plus-minus) 9, and 164 (plus-minus) 15 mg/(L·d). Furthermore, by adopting a fed-batch cultivation strategy, a maximum DW and concentrations of total saponin and polysaccharide in the 30-L CIB were enhanced to 30.3 (plus-minus) 1.0, 2.1 (plus-minus) 0.1, and 3.5 (plus-minus) 0.2 g/L with their corresponding productivity of 1467 (plus-minus) 87, 102 (plus-minus) 13, and 179 (plusminus) 18 mg/(L.d), respectively. The work suggests that the CIB may have great potential in large-scale high-density plant cell cultures for efficient production of useful secondary metabolites.