Silkworm pupae globulin promotes Cordyceps militaris fermentation: Regulation of metabolic pathways enhances cordycepin synthesis and extends the synthesis phase

Cordyceps militaris is known for its production of cordycepin, which possesses various biological activities. Silkworm pupae serve as the hosts for Cordyceps militaris, thereby facilitating the synthesis of cordycepin. In this work, the components of silkworm pupae were isolated and used as regulatory factors to promote liquid fermentation of C. militaris to produce cordycepin. Compared with lipids, crude proteins in silkworm pupae are more capable of promoting cordycepin synthesis. Notably, when four proteins (albumin, globulin, gladin and gluten) isolated from crude proteins were added to the fermentation system according to their extraction rates, only globulin had a similar promotional effect as crude protein. In addition, supplementation with 3.31 g/L globulin extended the cordycepin synthesis stage for 6 days, during which the expression level of cns1-4, genes related to cordycepin synthesis, were significantly up-regulated. Transcriptome analysis of the metabolic pathway of C. militaris after globulin supplementation revealed that the upregulation of glucose metabolism and energy metabolism played a crucial role in extending the synthesis stage of cordycepin to 2.5 times. Silkworm pupae globulin is the main functional factor regulating the synthesis of cordycepin in C. militaris, and is a potential material for industrial production of cordycepin.