A Novel Complementary Pathway of Cordycepin Biosynthesis in Cordyceps militaris

Abstract

Abstract We determined whether there exists a complementary pathway of cordycepin biosynthesis in wild-type Cordyceps militaris, cordycepin-high-producing strain C. militaris GYS60, and cordycepin-low-producing strain C. militaris GYS80. Differentially expressed genes were identified through transcriptomes of the three strains. Compared with C. militaris, in GYS60 and GYS80, we identified 145 and 470 upregulated and 96 and 594 downregulated genes. Compared with GYS80, in GYS60, we identified 306 upregulated and 207 downregulated genes. GO analysis revealed that upregulated genes were mostly involved in detoxification, antioxidant, and molecular transducer in GYS60. By COG and KEGG analyses, eight genes were significantly upregulated; five genes related to purine metabolism, one to ATP production, one to secondary metabolite transport, and one to RNA degradation. In GYS60, cordycepin was significantly increased by upregulation of ATP production, which promoted 3',5'-cyclic AMP production. Cyclic AMP accelerated 3'-AMP accumulation, and cordycepin continued to be synthesized and exported. We verified the novel complementary pathway by adding the precursor adenosine and analyzing the expression of four key genes involved in the main pathway of cordycepin biosynthesis. Upon adenosine addition, cordycepin was increased by 51.2% and 10.1%, respectively, in C. militaris and GYS60. Four genes in the main pathway in GYS60 were not upregulated.