Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand
Ratchaprapa Ruengsang
Bioinformatics and Systems Biology Program, School of Bioresources and Technology and School of Information Technology, King Mongkut’s University of Technology Thonburi (Bang Khun Thian), Bangkok 10150, Thailand
Roypim Thananusak
Omics Center for Agriculture, Bioresources, Food, and Health, Kasetsart University (OmiKU), Bangkok 10900, Thailand
Teeraphan Laomettachit
Bioinformatics and Systems Biology Program, School of Bioresources and Technology and School of Information Technology, King Mongkut’s University of Technology Thonburi (Bang Khun Thian), Bangkok 10150, 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
Treenut Saithong
Bioinformatics and Systems Biology Program, School of Bioresources and Technology and School of Information Technology, King Mongkut’s University of Technology Thonburi (Bang Khun Thian), Bangkok 10150, Thailand
Wanwipa Vongsangnak
Omics Center for Agriculture, Bioresources, Food, and Health, Kasetsart University (OmiKU), Bangkok 10900, Thailand
The genome-scale metabolic model (GSMM) of Cordyceps militaris provides a comprehensive basis of carbon assimilation for cell growth and metabolite production. However, the model with a simple mass balance concept shows limited capability to probe the metabolic responses of C. militaris under light exposure. This study, therefore, employed the transcriptome-integrated GSMM approach to extend the investigation of C. militaris’s metabolism under light conditions. Through the gene inactivity moderated by metabolism and expression (GIMME) framework, the iPS1474-tiGSMM model was furnished with the transcriptome data, thus providing a simulation that described reasonably well the metabolic responses underlying the phenotypic observation of C. militaris under the particular light conditions. The iPS1474-tiGSMM obviously showed an improved prediction of metabolic fluxes in correlation with the expressed genes involved in the cordycepin and carotenoid biosynthetic pathways under the sucrose culturing conditions. Further analysis of reporter metabolites suggested that the central carbon, purine, and fatty acid metabolisms towards carotenoid biosynthesis were the predominant metabolic processes responsible in light conditions. This finding highlights the key responsive processes enabling the acclimatization of C. militaris metabolism in varying light conditions. This study provides a valuable perspective on manipulating metabolic genes and fluxes towards the target metabolite production of C. militaris.
