Raethong Nachon, Wang Hao, Nielsen Jens, Vongsangnak Wanwipa
Interdisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok, Thailand.
Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Comput Struct Biotechnol J. 2019 Nov 26;18:1-8. doi: 10.1016/j.csbj.2019.11.003. eCollection 2020.
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: https://github.com/sysbiomics/-GEM.
是一种昆虫病原真菌，在亚洲常被用作源于古老智慧发展而来的传统药物。目前，来自该真菌的虫草素在医学应用中备受关注。然而，该真菌的细胞生长以及与虫草素产生的关联仍知之甚少。为了探索该真菌作为医学和生物技术应用中潜在细胞工厂的代谢情况，本研究基于其基因组内容和生理数据，开发了一个高质量的基因组规模代谢模型，即NR1329。该模型总共包括4个不同细胞区室中的1329个基因、1821个生化反应和1171个代谢物。其生长模拟结果与不同碳源上的实验数据吻合良好。NR1329进一步被用于使用一种新颖的方法POPCORN来优化生长和过量生产虫草素，以合理设计合成培养基。除了高质量的GEM NR1329外，所提出的POPCORN方法成功地用于合理设计一种碳氮比为8:1的最佳合成培养基，以提高虫草素产量3.5倍。因此，本研究为该真菌的生理学提供了新的见解，并突出了一种潜在的由GEM驱动的合成培养基设计和代谢工程应用方法。NR1329和POPCORN方法可在GitHub仓库获取：https://github.com/sysbiomics/-GEM 。
