Optimizing cultivation of Cordyceps militaris for fast growth and cordycepin overproduction using rational design of synthetic media
Journal article, 2020

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.

Cordycepin

Systems biology

Synthetic media design

Cordyceps militaris

Genome-scale modeling

Author

Nachon Raethong

Kasetsart University

Hao Wang

Wallenberg Lab.

CSBI

Chalmers, Biology and Biological Engineering

National Bioinformatics Infrastructure Sweden (NBIS)

Science for Life Laboratory (SciLifeLab)

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Technical University of Denmark (DTU)

Wanwipa Vongsangnak

Kasetsart University

Soochow University

Computational and Structural Biotechnology Journal

2001-0370 (eISSN)

Vol. 18 1-8

Subject Categories

Chemical Process Engineering

Bioinformatics (Computational Biology)

Software Engineering

DOI

10.1016/j.csbj.2019.11.003

More information

Latest update

2/20/2020