Construction of Light-Responsive Gene Regulatory Network for Growth, Development and Secondary Metabolite Production in Cordyceps militaris

SIMPLE SUMMARY: Cordyceps militaris is an edible fungus that has been long used in traditional medicine. A large body of research has provided evidence of the medicinal properties of C. militaris extract and its demand has been increasing over the years. This study aims to construct and understand the light-responsive gene regulatory network of the fungi by combining the transcription factor (TF)-target gene interactions with the transcriptomic analysis of C. militaris under a light-programming condition. The study identified several key TFs and their gene targets that regulate growth, development and secondary metabolite production in the fungi under specific light conditions. ABSTRACT: Cordyceps militaris is an edible fungus that produces many beneficial compounds, including cordycepin and carotenoid. In many fungi, growth, development and secondary metabolite production are controlled by crosstalk between light-signaling pathways and other regulatory cascades. However, little is known about the gene regulation upon light exposure in C. militaris. This study aims to construct a gene regulatory network (GRN) that responds to light in C. militaris. First, a genome-scale GRN was built based on transcription factor (TF)-target gene interactions predicted from the Regulatory Sequence Analysis Tools (RSAT). Then, a light-responsive GRN was extracted by integrating the transcriptomic data onto the genome-scale GRN. The light-responsive network contains 2689 genes and 6837 interactions. From the network, five TFs, Snf21 (CCM_04586), an AT-hook DNA-binding motif TF (CCM_08536), a homeobox TF (CCM_07504), a forkhead box protein L2 (CCM_02646) and a heat shock factor Hsf1 (CCM_05142), were identified as key regulators that co-regulate a large group of growth and developmental genes. The identified regulatory network and expression profiles from our analysis suggested how light may induce the growth and development of C. militaris into a sexual cycle. The light-mediated regulation also couples fungal development with cordycepin and carotenoid production. This study leads to an enhanced understanding of the light-responsive regulation of growth, development and secondary metabolite production in the fungi.