Screening of a Double Auxotrophic Cordyceps militaris Mutant and Its High Fermentation Yield of Cordycepin
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Abstract:
Cordycepin, with a variety of medical and health benefits, is one of the key bioactive compounds in Cordyceps militaris. However, the low fermentation yield restricts its industrial production and applications. To enhance the yield of cordycepin, a xanthine-guanine double auxotrophic mutant, xan-gua--c, was obtained by ultrasound mutagenesis combined with diethyl sulfate treatments, followed by directional screening, and its yield of cordycepin was improved to 1.76 g/L on the 20th day of batch fermentation, about 40% higher than that of the control. The effects of structural analogs of cordycepin on the cordycepin production capacity of the mutant were then investigated. The results showed that the addition of 1.0 g/L adenosine and 1.0 g/L adenine could improve the production of cordycepin (on the 20th day) by 33.5% (to 2.35 g/L) and 103.5% (to 3.59 g/L), respectively, compared with that of the control. Metabolic pathway analysis indicated that there might be two metabolic pathways used to synthesize cordycepin from adenine or adenosine. The two metabolic processes might overlap, and blocking the anabolism of xanthine and guanine might be an effective strategy to promote Cordyceps militaris to accumulate cordycepin.