Comparative Transcriptomic Responses Directed Towards Reporter Metabolic Routes of Mucor circinelloides WJ11 for Growth Adaptation and Lipid Overproduction

Research into the cellular metabolic adaptations of Mucor circinelloides has gained significant interest due to its capability for lipid production, which has critical industrial applications. To address the regulatory mechanisms at the systems level, this study aimed to explore the global metabolic responses associated with lipid production in high and low lipid-producing strains of M. circinelloides, WJ11 and CBS277.49, respectively, through comparative transcriptome analysis and genome-scale model-driven analysis. The transcriptome analysis of expressed genes in M. circinelloides WJ11 (6398 genes), and CBS277.49 (6008 genes) were analyzed and compared. The results revealed 2811 significantly differentially expressed genes and highlighted strain-dependent differences in growth behavior and lipid production of M. circinelloides at the fast-growing stage, driven by transcriptional regulation across key metabolic pathways. Through genome-scale model-driven analysis, we identified 20 significant reporter metabolites that provide insights into the mechanisms employed by the WJ11 strain to optimize growth for lipid production in the subsequent lipid-accumulating stage. These interplay mechanisms are primarily involved in glycolysis, the TCA cycle, leucine metabolism, energy metabolism, and one-carbon metabolism towards lipid metabolism. These findings provide valuable insights into the regulatory mechanisms underlying lipid production in Mucor and highlight potential pathways for genetic and physiological optimization in high lipid-producing strains like WJ11. This research advances our understanding of how metabolic networks are interconnected and how they can be leveraged for more efficient lipid overproduction.