Poly-pathways metabolomics for high-yielding cordycepin of Cordyceps militaris

Cordycepin is an important quality control marker in Cordyceps militaris. This study aimed to explain the metabolic mechanisms for high-yielding cordycepin of C. militaris. In this study, high-yielding strains of cordycepin were obtained by ultraviolet mutagenesis, and the polysaccharide and protein contents were also changed. In high-yielding strains, the protein content significantly increased, whereas the polysaccharide content decreased. Simultaneously, metabolic differences for high- and low-yielding cordycepin strains were detected by metabolomics. Metabolomics results showed that the relative content of most metabolites decreased in high-yielding cordycepin strains. Various metabolic pathways have been altered in high-yielding cordycepin strains, such as the citric acid cycle, purine metabolism, and pyrimidine metabolism, leading to an increase in cordycepin content. In addition, changes in metabolic poly-pathways related to polysaccharide and protein synthesis, such as galactose metabolism and amino acid metabolism, promoted an increase in cordycepin content. This study analyzes the high yield of cordycepin in C. militaris at the metabolic level and provides a theoretical basis for further increasing cordycepin content.