Optimization for High-Yield Adenosine Production from Cordyceps militaris in Submerged Fermentation

Cordyceps militaris, a prized medicinal fungus in East Asian traditional medicine, is renowned for its bioactive compound, adenosine. This compound exhibits diverse pharmacological properties, including anti-aging, skin regeneration, wrinkle reduction, and hair growth promotion. To optimize adenosine production, we employed a Taguchi experimental design to evaluate the impact of key factors with the following conditions: fungal strains (C. militaris SH01, C. militaris ATCC 34165, and hybrid strain of C. militaris SH01 and C. militaris ATCC 34165), glucose concentration (20, 40, and 60 g/L), yeast extract concentration (5, 10, and 20 g/L), and initial pH (4.0, 5.5, and 7.0). The optimization experiments were carried out in 250-mL shaking flasks at 110 rpm at 25 °C. Among the tested strains, C. militaris SH01 demonstrated superior adenosine production under predicted optimal conditions from the Taguchi method (Qualitek-4 software): 40 g/L glucose, 20 g/L yeast extract, and an initial pH of 4.0. This resulted in a maximum adenosine yield of 8.662±0.269 mg/g and a productivity of 2.495±0.077 mg/g.d, surpassing the predicted values by 44%. However, when scaled up to a 5-L shaking flask, adenosine productivity decreased to 1.849±0.094 mg/g.d. Our findings provide valuable insights for enhancing adenosine production from C. militaris, paving the way for its potential application in various industries, including healthcare, food, and cosmetics.