Enhanced production of cordycepin by surface culture using the medicinal mushroom Cordyceps militaris

The methods for increasing the production of cordycepin (3′-deoxyadenosine), which is a kind of nucleoside analogue, were investigated by a surface culture of Cordyceps militaris NBRC 9787 using liquid medium. As a result of adding various compounds such as purine biosynthesis-related compounds, coenzymes and surfactant to the basal medium for the purpose of enhancing the cordycepin production, glycine, l-aspartic acid, l-glutamine, adenine and adenosine were shown to be effective additives. The most preferable condition of the additives was the combination of 1 g/l of adenine and 16 g/l of glycine, and the maximum cordycepin production reached 2.5 g/l, which corresponds to 4.1 times that in the basal medium, and this value was higher compared to other reports. As a more efficient method, the repeated batch operation was shown to be practicable, and the productivity by the repeated batch operation in the optimal medium reached 0.19 g/(l d), which corresponds to 5.5 times that by the batch operation in the basal medium. The nucleic acid-related compounds produced by the surface culture were also analyzed. The results indicated that about 97% of the cordycepin synthesized by C. militaris was excreted into the culture medium, and the production of cordycepin and guanine might be linked to each other.