Improvement of cordycepin production by an isolated Paecilomyces hepiali mutant from combinatorial mutation breeding and medium screening.

Cordycepin is a major bioactive compound found in Cordyceps sinensis that exhibits a broad spectrum of biological activities. Here a Paecilomyces hepiali OR-1 strain was initially isolated from plateau soil for the bioproduction of cordycepin. Subsequently, strain modification including Co γ-ray and ultraviolet irradiation were employed to increase the cordycepin titer, resulted in a high-yield mutant strain P. hepiali ZJB18001 with the cordycepin content of 0.61 mg/g, showing a 2.3-fold to that from the wild strain (0.26 mg/g). Furthermore, medium screening based on Box-Behnken design and the response surface methodology facilitated the enhancement of cordycepin yield to the value of 0.96 mg/g at 25 °C for 5 days in submerged cultivation with an optimized medium composition. The high cordycepin yield, rapid growth rate and stable genetic characteristics of P. hepiali ZJB18001 are beneficial in terms of costs and time for the industrialization of cordycepin production.