Effect of multiple factors on accumulation of nucleosides and bases in Cordyceps militaris

In order to improve the accumulation of valuable metabolites (3′-deoxyadenosine, adenosine, guanosine, cytidine, uridine, adenine and uracil) in Cordyceps militaris, multiple factors such as carbon sources, nitrogen sources, metal ions and fermentation duration were investigated in liquid shake flasks. Using both potato broth and glucose as carbon sources were found to facilitate the production of nucleosides and bases most, and 2% of glucose was the most suitable initial level. Mixture of 0.3% yeast extract with 0.3% peptone was the best selection of nitrogen sources and supplementing with 0.1 mmol/L Mn2+ achieved the maximum biomass and biosynthesis of nucleosides and bases among all investigated metal ions. The most suitable harvest time for C. militaris was found to be the 6th day, because the production of 3′-deoxyadenosine, adenosine and uridine began to speed up from the later exponential growth phase until the 6th day. Finally, under optimal culture conditions, the contents of 3′-deoxyadenosine, adenosine, guanosine, cytidine, uridine, adenine and uracil were increased to 0.212 ± 0.014 mg/g, 5.05 ± 0.31 mg/g, 4.03 ± 0.30 mg/g, 0.556 ± 0.029 mg/g, 6.39 ± 0.33 mg/g, 0.208 ± 0.016 mg/g and 0.437 ± 0.027 mg/g, respectively.