Study on extracellular production of cordycepin and pentostatin by Cordyceps militaris under liquid surface fermentation

Abstract

Cordyceps militaris is widely used in traditional medicine and as a food source. This fungus is capable of producing cordycepin and pentostatin, two bioactive compounds with antimicrobial, immunomodulatory, and cytotoxic activities against cancer cells. However, C. militaris is predominantly produced in the form of fruiting bodies for use as raw material. Recently, liquid-state surface fermentation has shown considerable potential for enhancing extracellular metabolite production in fungi. This study selected three C. militaris strains (HL8, BN25.2, and TN25.1) with high extracellular production of cordycepin and pentostatin. All three strains demonstrated stable extracellular production of cordycepin and pentostatin over five consecutive generations. Furthermore, the study identified suitable conditions for surface liquid-state fermentation of C. militaris, including the use of white LED light, a fermentation medium containing glucose as the carbon source and tryptone as the nitrogen source, an initial pH of 6, and a fermentation duration of 45 days. Under the suitable fermentation conditions, the average extracellular production of cordycepin by strains HL8, BN25.2, and TN25.1 reached 1220, 1415, and 1225 mg/l, respectively, while pentostatin production reached 45.6, 35.6, and 37.6 mg/l fermentation broth. The fermentation broth represents a promising source of raw material for the development of food and pharmaceutical products.