Dissecting Holistic Metabolic Acclimatization of <i>Mucor circinelloides</i> WJ11 Defective in Carotenoid Biosynthesis

<i>Mucor circinelloides</i> WJ11 is a lipid-producing strain with industrial potential. A holistic approach using gene manipulation and bioprocessing development has improved lipid production and the strain’s economic viability. However, the systematic regulation of lipid accumulation and carotenoid biosynthesis in <i>M. circinelloides</i> remains unknown. To dissect the metabolic mechanism underlying lipid and carotenoid biosynthesis, transcriptome analysis and reporter metabolites identification were implemented between the wild-type (WJ11) and <i>ΔcarRP</i> WJ11 strains of <i>M. circinelloides</i>. As a result, transcriptome analysis revealed 10,287 expressed genes, with 657 differentially expressed genes (DEGs) primarily involved in amino acid, carbohydrate, and energy metabolism. Integration with a genome-scale metabolic model (GSMM) identified reporter metabolites in the <i>ΔcarRP</i> WJ11 strain, highlighting metabolic pathways crucial for amino acid, energy, and nitrogen metabolism. Notably, the downregulation of genes associated with carotenoid biosynthesis and acetyl-CoA generation suggests a coordinated relationship between the carotenoid and fatty acid biosynthesis pathways. Despite disruptions in the carotenoid pathway, lipid production remains stagnant due to reduced acetyl-CoA availability, emphasizing the intricate metabolic interplay. These findings provide insights into the coordinated relationship between carotenoid and fatty acid biosynthesis in <i>M. circinelloides</i> that are valuable in applied research to design optimized strains for producing desired bioproducts through emerging technology.