Optimizing cultivation of Cordyceps militaris for fast growth and cordycepin overproduction using rational design of synthetic media

摘要

is an entomopathogenic fungus which is often used in Asia as a traditional medicine developed from age-old wisdom. Presently, cordycepin from is a great interest in medicinal applications. However, cellular growth of and the association with cordycepin production remain poorly understood. To explore the metabolism of as potential cell factories in medical and biotechnology applications, this study developed a high-quality genome-scale metabolic model of , NR1329, based on its genomic content and physiological data. The model included a total of 1329 genes, 1821 biochemical reactions, and 1171 metabolites among 4 different cellular compartments. Its growth simulation results agreed well with experimental data on different carbon sources. NR1329 was further used for optimizing the growth and cordycepin overproduction using a novel approach, POPCORN, for rational design of synthetic media. In addition to the high-quality GEM NR1329, the presented POPCORN approach was successfully used to rationally design an optimal synthetic medium with C:N ratio of 8:1 for enhancing 3.5-fold increase in cordycepin production. This study thus provides a novel insight into physiology and highlights a potential GEM-driven method for synthetic media design and metabolic engineering application. The NR1329 and the POPCORN approach are available at the GitHub repository: .