Sustainable Production of Cordycepin and Adenosine from Cordyceps militaris Using Agro-Industrial Byproducts
Keywords:
agro-industrial byproducts, medicinal mushrooms, sustainability, bioactive compoundsAbstract
Agro-industrial byproducts are abundant, low-cost resources with strong potential for bioconversion into high-value bioactive compounds. This study explored the use of soybean hulls (SB-H), sugarcane bagasse (SC-B), and rice husk (RH-K) as alternative substrates for the cost-effective cultivation of Cordyceps militaris under solid-state fermentation, with jasmine brown rice (JBR) serving as the control. The results indicated that SB-H produced a biomass yield of 3.04 ± 0.06 g dry weight (DW), which was not significantly different from JBR (3.07 ± 0.06 g DW). However, SB-H significantly (p ≤ 0.05) enhanced the production of bioactive compounds, yielding cordycepin at 7.76 ± 0.26 mg/g DW, representing a 22.40% increase over the control, and adenosine at 0.47 ± 0.02 mg/g DW. In addition, cultivation with SB-H reduced the production cost per gram of dry biomass by 7.54%. Analysis of spent mushroom substrates (SMS) revealed high levels of residual compounds, with SB-H containing the highest residual cordycepin content (6.83 ± 0.16 mg/g DW), while SC-B contained the highest residual adenosine content (0.37 ± 0.02 mg/g DW), highlighting their potential for secondary utilization. These findings demonstrate that agro-industrial byproducts, particularly soybean hulls, can serve as sustainable and efficient alternative substrates for the cultivation of C. militaris, offering comparable biomass yield, enhanced bioactive compound production, cost reduction, and support for circular economy practices in medicinal mushroom cultivation.
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Priyanka, G., Singiri, J. R., Adler-Agmon, Z., Sannidhi, S., Daida, S., Novoplansky, N., and Grafi, G. (2024). Detailed analysis of agro-industrial byproducts/wastes to enable efficient sorting for various agro-industrial applications. Bioresources and Bioprocessing, 11(1), Article 45.
Rațu, R. N., Veleșcu, I. D., Stoica, F., Usturoi, A., Arsenoaia, V. N., Crivei, I. C., Postolache, A. N., Lipșa, F. D., Filipov, F., Florea, A. M., Chițea, M. A., and Brumă, I. S. (2023). Application of agri-food by-products in the food industry. Agriculture, 13(8), Article 1559.
Ashraf, S. A., Elkhalifa, A. E. O., Siddiqui, A. J., Patel, M., Awadelkareem, A. M., Snoussi, M., Ashraf, M. S., Adnan, M., and Hadi, S. (2020). Cordycepin for health and wellbeing: A potent bioactive metabolite of an entomopathogenic cordyceps medicinal fungus and its nutraceutical and therapeutic potential. Molecules, 25(12), Article 2735.
Elkhateeb, W., Daba, G., Thomas, P., and Wen, T.-C. (2019). Medicinal mushrooms as a new source of natural therapeutic bioactive compounds. Egyptian Pharmaceutical Journal, 18(2), 88-101.
Trung, N. Q., Dat, N. T., Anh, H. N., Tung, Q. N., Nguyen, V. T. H., Van, H. N. B., Van, N. M. N., and Minh, T. N. (2024). Substrate influence on enzymatic activity in Cordyceps militaris for health applications. Chemistry, 6, 517-530.
Wen, T.-C., Li, G. R., Kang, J.-C., Kang, C., and Hyde, K. (2014). Optimization of solid-state fermentation for fruiting body growth and cordycepin production by Cordyceps militaris. Chiang Mai Journal of Science, 41, 858-872.
Tao, S. X., Xue, D., Lu, Z. H., and Huang, H. L. (2020). Effects of substrates on the production of fruiting bodies and the bioactive components by different Cordyceps militaris strains (Ascomycetes). International Journal of Medicinal Mushrooms, 22(1), 55-63.
Borde, M., and Singh, S. K. (2023). Enhanced production of cordycepin under solid-state fermentation of Cordyceps militaris by using combinations of grains/substrates. Brazilian Journal of Microbiology, 54(4), 2765-2772.
Lin, Q., Long, L., Wu, L., Zhang, F., Wu, S., Zhang, W., and Sun, X. (2017). Evaluation of different agricultural wastes for the production of fruiting bodies and bioactive compounds by medicinal mushroom Cordyceps militaris. Journal of the Science of Food and Agriculture, 97(10), 3476-3480.
Pintathong, P., Chomnunti, P., Sangthong, S., Jirarat, A., and Chaiwut, P. (2021). The feasibility of utilizing cultured Cordyceps militaris residues in cosmetics: Biological activity assessment of their crude extracts. Journal of Fungi (Basel), 7(11), Article 973.
Jędrejko, K., Kała, K., Sułkowska-Ziaja, K., Krakowska, A., Zięba, P., Marzec, K., Szewczyk, A., Sękara, A., Pytko-Polończyk, J., and Muszyńska, B. (2022). Cordyceps militaris-fruiting bodies, mycelium, and supplements: Valuable component of daily diet. Antioxidants (Basel), 11(10), Article 1861.
Jędrejko, K. J., Lazur, J., and Muszyńska, B. (2021). Cordyceps militaris: An overview of its chemical constituents in relation to biological activity. Foods, 10(11), Article 2634.
Dunn, J., and Grider, M. H. (2023). Physiology, adenosine triphosphate. Treasure Island (FL): StatPearls Publishing.
Zhang, H., Yang, J., Luo, S., Liu, L., Yang, G., Gao, B., Fan, H., Deng, L., and Yang, M. (2024). A novel complementary pathway of cordycepin biosynthesis in Cordyceps militaris. International Microbiology, 27(4), 1009-1021.
Pang, F., Wang, L., Jin, Y., Guo, L., Song, L., Liu, G., and Feng, C. (2018). Transcriptome analysis of Paecilomyces hepiali at different growth stages and culture additives to reveal putative genes in cordycepin biosynthesis. Genomics, 110(3), 162-170.
Gregori, A., (2014). Cordycepin production by Cordyceps militaris cultivation on spent brewery grains. Acta Biologica Slovenica, 57(2), 45-52.
Raethong, N., Wang, H., Nielsen, J., and Vongsangnak, W. (2019). Optimizing cultivation of Cordyceps militaris for fast growth and cordycepin overproduction using rational design of synthetic media. Computational and Structural Biotechnology Journal, 18, 1-8.
Zou, G., Li, B., Wang, Y., Yin, X., Gong, M., Shang, J., Wei, Y., Li, X., and Bao, D. (2021). Efficient conversion of spent mushroom substrate into high value-added anticancer drug pentostatin with engineered Cordyceps militaris. Green Chemistry, 23(24), 10030-10038.
Kontogiannatos, D., Koutrotsios, G., Xekalaki, S., and Zervakis, G. I. (2021). Biomass and cordycepin production by the medicinal mushroom Cordyceps militaris-A review of various aspects and recent trends towards the exploitation of a valuable fungus. Journal of Fungi (Basel), 7(11), Article 986.
Barbosa, F. F., Tokach, M. D., DeRouchey, J. M., Goodband, R. D., Nelssen, J. L., and Dritz, S. S. (2008). Variation in chemical composition of soybean hulls. Kansas Agricultural Experiment Station Research Reports, 0(10). https://doi.org/10.4148/2378-5977.7001
Chang, Y., Liu, X., Jiao, Y., and Zheng, X. (2024). Improved cordycepin production by Cordyceps militaris using corn steep liquor hydrolysate as an alternative protein nitrogen source. Foods, 13(15), Article 813.
Shrestha, B., Zhang, W., Zhang, Y., and Liu, X. (2012). The medicinal fungus Cordyceps militaris: Research and development. Mycological Progress, 11(3), 599-614.
Phoungthong, K., Aiphuk, W., Maneerat, T., Suwunwong, T., Choto, P., and Chomnunti, P. (2022). Utilization of corncob biochar in cultivation media for cordycepin production and biomass of Cordyceps militaris. Sustainability, 14(15), Article 9362.
Ma, X., Yan, S., and Wang, M. (2025). Spent mushroom substrate: A review on present and future of green applications. Journal of Environmental Management, 373, Article 123970.
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