Cordycepin is one of the most important bioactive compounds; the low productivity and long production cycle of cordycepin are barriers to its commercialization. The optimal media for cordycepin production by Cordyceps militaris BCC 2819 and Cordyceps cicadae BCC 19788, which are potent cordycepin-producing-fungal strains, were determined through statistical experiments. Six nutrients including glucose, adenine, glycine, alanine, casein hydrolysate and vitamin solution were found to influence the cordycepin production by C. militaris BCC 2819, while the same factors were found for the cordycepin production by C. cicadae BCC 19788 except glucose that was replaced by ammonium sulfate. The highest cordycepin production of 1,176.69 ± 263.33 mg/L was obtained by C. militaris BCC 2819 using the central composite design. The highest cordycepin production of 4,259.63 ± 224.20 mg/L was obtained by C. cicadae BCC 19788 using the central composite design. Cordycepin production in 5-L fed-batch fermentation by C. militaris BCC 2819 and C. cicadae BCC 19788 using optimized medium reached maximum production levels of 3,112.50 and 3,587.10 mg/L, respectively, accounted for more than 1.2-fold compared to those in batch fermentation. Furthermore, the highest levels of the bioactive compounds; exopolysaccharide, adenosine and mannitol produced by C. militaris BCC 2819 were 43.90 ± 2.51 g/L, 2,897.40 ± 382.47 mg/L and 5,981.10 ± 254.72 mg/L, respectively. The highest levels of the bioactive compounds; exopolysaccharide, adenosine and mannitol produced by C. cicadae BCC 19788 were 38.10 ± 2.84 g/L, 3,78520 ± 165.70 mg/L and 6,100.20 ± 191.14 mg/L, respectively. These results demonstrated the new isolates produced high amounts of bioactive compounds, especially cordycepin. Interestingly, this process can be applied for cordycepin production for future applications or scale-up studies.
Key words: Batch fermentation, cordycepin, Cordyceps militaris, fed-batch fermentation, Cordyceps cicadae, optimization.
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