Biotechnology and Bioprocess Engineering 2023; 28(3): 406-418  
Dissecting Metabolic Regulation in Mycelial Growth and Fruiting Body Developmental Stages of Cordyceps militaris through Integrative Transcriptome Analysis
Roypim Thananusak, Kobkul Laoteng, Nachon Raethong, Mattheos Koffas, and Wanwipa Vongsangnak
Roypim Thananusak, Mattheos Koffas
Interdisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
Kobkul Laoteng
Industrial Bioprocess Technology Research Team, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand
Nachon Raethong
Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand
Mattheos Koffas
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA
Wanwipa Vongsangnak*
Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
Omics Center for Agriculture, Bioresources, Food, and Health, Kasetsart University (OmiKU), Bangkok 10900, Thailand
Tel: +66-2-562-5555 ext. 647818; Fax: +66-2942-8290
Received: July 5, 2022; Revised: September 4, 2022; Accepted: September 20, 2022; Published online: June 30, 2023.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Dissecting the cellular metabolism of Cordyceps militaris is important for the efficient production of bioactive compounds of a target with medicinal and industrial applications. However, the metabolic functions during developmental stages in this fungus at a system level are still unexplored. In this study, we aimed to reveal the metabolic functions and regulation of C. militaris TBRC6039 relevant to its developmental stages, including mycelial growth (MY) and fruiting body (FB) stages through integrative transcriptome analysis. The transcriptome analysis showed that 9,256 genes of C. militaris were expressed in both stages. Of them, 1,877 genes, residing primarily in the cell division cycle and amino acid, carbohydrate, and lipid metabolisms, exhibited significant differences in transcript levels between the MY and FB stages. Through integration with genome-scale networks analysis, the unique reporter metabolites (e.g., α-D-glucose, β-D-glucose, D-galactose, triacylglycerol, and diacylglycerol) and key regulators (e.g., AtfA, Atf2, and Yap1 transcription factors) were identified in C. militaris when grown at FB stage, linking to up-regulation of the metabolic genes involved in galactose and polysaccharide metabolisms, as well as glycerolipid and glycerophospholipid biosynthesis. Moreover, the high cordycepin content is related to the upregulated genes in lipid metabolism during the FB stage. Our findings suggest that the transcriptional regulation of these metabolic pathways played a crucial role in specific developmental stages of C. militaris. This study serves for cultivation process improvement for overproduction of valuable metabolites in C. militaris through an emerging systems and synthetic biology approach.
Keywords: Cordyceps militaris, fruiting body, transcriptome analysis, reporter metabolite, transcription factor

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