Enhancement of Cordycepin Production in Cordyceps militaris by the Influence of Edible Insects and Medicinal Plants 

Enhancement of Cordycepin Production in Cordyceps militaris by the Influence of Edible Insects and Medicinal Plants 

Ayman Turk1, Mohamed A.A. Abdelhamid2, Solip Lee1, Sang Won Yeon1, Se Hwan Ryu1, Yoo Kyong Han3, Young Jun Kim3, Sung Min Ko1,4, Beom Seok Kim1,4, Seung Pil Pack2, Bang Yeon Hwang1, Ki Yong Lee3, and Mi Kyeong Lee1,*

1College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea

2Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Republic of Korea

3College of Pharmacy, Korea University, Sejong 47236, Republic of Korea

4C&G Agricultural Association, Sejong 30067, Republic of Korea

                                                           *Email: aymanturk@chungbuk.ac.kr

Cordycepin, also known as 3′-deoxyadenosine, is a key component in Cordyceps militaris with several pharmacological properties. Natural C. militaris cannot meet market demand due to its poor cordycepin production. Using six edible insects and medicinal plants as substrates, the optimal Cordyceps culture conditions for cordycepin production were investigated. Allomyrina dichotoma produced 34 times more cordycepin than Bombyx mori pupae. Fat content in insects is critical for cordycepin production. Especially, oleic acid concentration correlated positively with cordycepin synthesis. In Cordyceps growing on A. dichotoma, cns1 and cns2 genes implicated in cordycepin biosynthesis were more highly expressed than in other insects. Oleic acid boosted cordycepin production and cns1 and cns2 transcription. However, eight medicinal plants were combined with Cordyceps culture substrates to boost cordycepin. The addition of 25% Mori Folium quadrupled cordycepin content. Adenosine deaminase (ADA) controls adenosine and deoxyadenosine deamination, and its inhibitors have anti-proliferative and anti-inflammatory actions. The inhibitory activity of a medicinal plant on ADA was assessed using spectrophotometric analysis, using cordycepin as a substrate, due to its conversion to 3′-deoxyinosine by ADA. Mori Folium, Curcumae Rhizoma, Saururi Herba, and Angelicae Gigas Radix reduced ADA activity as predicted. Molecular docking analysis also showed the correlation between ADA and the major components of these medicinal plants. Conclusively, our research suggests a new strategy of using insects and medicinal plants to enhance cordycepin production in C. militaris.