Cordyceps militaris is an entomopathogenic fungus which is often used in Asia as a traditional medicine developed from age-old wisdom. Presently, cordycepin from C. militaris is a great interest in medicinal applications. However, cellular growth of C. militaris and the association with cordycepin production remain poorly understood. To explore the metabolism of C. militaris as potential cell factories in medical and biotechnology applications, this study developed a high-quality genome-scale metabolic model of C. militaris, iNR1329, 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 in silico growth simulation results agreed well with experimental data on different carbon sources. iNR1329 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 iNR1329, 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 C. militaris physiology and highlights a potential GEM-driven method for synthetic media design and metabolic engineering application. The iNR1329 and the POPCORN approach are available at the GitHub repository: https://github.com/sysbiomics/Cordyceps_militaris-GEM.

虫草是一种昆虫病原性真菌，在亚洲经常作为从古老智慧发展而来的传统药物使用。目前，从虫草蛹虫草是在医药应用了极大的兴趣。但是，细胞生长蛹虫草和与虫草素生产的关联仍然知之甚少。要探索的代谢蛹虫草作为医疗和生物技术应用的潜在细胞工厂，本研究开发的高品质基因组规模代谢模型蛹虫草，我NR1329，基于其基因组含量和生理数据。该模型在4个不同的细胞区室中总共包含1329个基因，1821个生化反应和1171个代谢产物。其计算机模拟生长结果与不同碳源的实验数据非常吻合。我NR1329进一步用于优化使用一种新颖的方法，爆米花，合成媒体的合理设计的生长和虫草素生产过剩。除了高质量的GEM i NR1329外，提出的POPCORN方法还被成功地用于合理设计C：N比为8：1的最佳合成培养基，以提高虫草素产量的3.5倍增长。因此，这项研究为into游梭菌提供了新颖的见解。生理学，并强调了由GEM驱动的潜在方法，可用于合成介质设计和代谢工程应用。在我NR1329和爆米花的方法是可以在GitHub的库：https://github.com/sysbiomics/ Cordyceps_militaris -GEM。