Improving Hypoxia Adaption Causes Distinct Effects on Growth and Bioactive Compounds Synthesis in an Entomopathogenic Fungus Cordyceps militaris

Abstract

Cordyceps militaris is an entomopathogenic fungus producing a variety of bioactive compounds. To meet the huge demand for medicinal and edible products, industrialized fermentation of mycelia and cultivation of stromata have been widely developed in China. The content of bioactive metabolites of C. militaris, such as cordycepin, is higher when cultivated on silkworm pupae than on rice or in broth. However, compared with other cultivation methods, C. militaris grows more slowly and accumulates less biomass. The hypoxic environment in pupa hemocoel is one of environmental factor which is not existed in other cultivation methods. It is suggested that hypoxia plays an important role on the growth and the synthesis of bioactive compounds in C. militaris. Here, we demonstrated that the distinct effects on the growth and synthesis of bioactive compounds employing different strategies of improving hypoxia adaption. The introduction of Vitreoscilla hemoglobin enhanced growth, biomass accumulation, and crude polysaccharides content of C. militaris. However, cordycepin production was decreased to 9–15% of the control group. Meanwhile, the yield of adenosine was increased significantly. Nonetheless, when the predicted bHLH transcription factor of sterol regulatory element binding proteins (SREBPs) was overexpressed in C. militaris to improve the hypoxia adaption of fungal cells, cordycepin content was significantly increased more than two-fold. These findings reveal the role of SREBPs on growth and bioactive compounds synthesis. And it also provides a scientific basis for rationally engineering strains and optimization strategies of air supply in cultivation and fermentation.

Potent Inhibitory Activities of the Adenosine Analogue Cordycepin on SARS-CoV-2 Replication

“…Recently, the natural cordycepin content was biologically increased to more than twofold in the entomopathogenic medicinal fungus C. militaris using newly designed techniques of optimized cultivation and fermentation, which significantly enhanced the biosynthesis of this precious bioactive metabolite . Cordycepin could also be easily synthesized from many readily available simple starting materials, such as d -glucose, d -xylose, and adenosine, using different chemical synthetic routes. , Cordycepin molecule is specifically a nucleosidic adenosine molecule that lacks only one hydroxyl group at the 3′ position of the five-membered ring of its ribose moiety (Figure ).…”

Current Advances in the Functional Genes of Edible and Medicinal Fungi: Research Techniques, Functional Analysis, and Prospects

“…Studies have shown that improving the hypoxic adaptability of the fungus contributes to the synthesis of the active substance. For example, our team overexpressed the predicted bHLH transcription factors of sterol regulatory element binding proteins (SREBPs) in vivo, which increased the cordycepin content more than two-fold, providing a scientific basis for optimizing the cultivation and fermentation gas supply strategy [227]. Xia et al [223] identified four highly homologous protein-coding genes (Cns1, Cns2, Cns3, and Cns4) in C. militaris.…”