Fermentation Optimization Of Protopanaxadiol Production By Saccharomyces Cerevisiae

Ginsenosides has received increasing attention as it exhibit diverse pharmacological activity,such as effects on antitumor,anti-inflammatory,anti-allergy,anti-hypertension and immune and central nervous system.Their precursor protopanaxadiol is also regarded as a promising high-value pharmaceutical compound.Protopanaxadiol was produced by Saccharomyces cerevisiae.Culture medium was optimization and the final medium consist of 20 g/L glucose,20 g/L peptone,10 g/L yeast extract powder,0.2 g/L adenine,0.2 g/L uracil,0.4 g/L lysine.Inoculum size was 5%.The yield of protopanaxadiol based on this medium was 0.380 g/L.In 5 L fermentation,pH was at 5.5.Three different feed strategies were tested,including a glucose pulse feed,a mixed glucose/ethanol feed and a restricted ethanol feed.The yield of 0.689 g/L was achieved with the restricted ethanol-feed-batch process.Protopanaxadiol production was increased to 1.3 g/L by feeding vitamin,trace metal and inorganic mineral solution into the medium.Besides,the influnce of two different height-diameter ratio to protopanaxadiol production was tested,which found that with the height-diameter ratio of 2:1,the yield of protopanaxadiol was 1.78 g/L,an inprovement of 85% compare to the yield with the height-diameter ratio of 1.25:1.In addtion,a two-phase extractive fermentation was performed in 5 L fermentor.Methyl oleate was used as the extractive solvent.After adding 10%(v/v)methyl oleate in 36 h,the protopanaxadiol production was decreased by 42.6%,and the yield of protopanaxadiol was 1.021 g/L.High cell-density fermentation was achieved by adenine feeding.Protopanaxadiol production was hold at a stable level of 4.25 g/L in fermontor,which is 15.9-fold than the initial yield in shake flask.