Simple Summary Oleaginous fungi are a promising candidate to produce microbial lipids as alternative sources for industrial applications. As lipids are intracellular metabolites with dynamic traits, the fungal ability in utilizing carbon sources for biomass and lipid production is significant in terms of production yield and economic feasibility. This study aimed to explore the metabolic regulation in lipogenesis of oleaginous Aspergillus oryzae BCC7051 at the transcriptional level. Through comparative transcriptome analysis, a set of differentially expressed genes (DEGs) between the xylose- and glucose-grown cultures (C5 and C6 cultures) at fast-growing and lipid-accumulating stages were identified and functionally categorized into transporter proteins and cellular processes. Combining with the growth and lipid phenotypes, the transcriptome results pointed to a crucial link between sugar assimilation, energy, lipid, and other metabolisms in A. oryzae for leveraging the metabolic flux from xylose to fatty acid and lipid biosynthesis in render the oleaginous features. This study provides a remarkable insight in guiding strain optimization and bioprocess development using renewable feedstocks from agroindustrial residues. Microbial lipid production with cost effectiveness is a prerequisite for the oleochemical sector. In this work, genome-wide transcriptional responses on the utilization of xylose and glucose in oleaginous Aspergillus oryzae were studied with relation to growth and lipid phenotypic traits. Comparative analysis of the active growth (t1) and lipid-accumulating (t2) stages showed that the C5 cultures efficiently consumed carbon sources for biomass and lipid production comparable to the C6 cultures. By pairwise comparison, 599 and 917 differentially expressed genes (DEGs) were identified in the t1 and t2 groups, respectively, in which the consensus DEGs were categorized into polysaccharide-degrading enzymes, membrane transports, and cellular processes. A discrimination in transcriptional responses of DEGs set was also found in various metabolic genes, mostly in carbohydrate, amino acid, lipid, cofactors, and vitamin metabolisms. Although central carbohydrate metabolism was shared among the C5 and C6 cultures, the metabolic functions in acetyl-CoA and NADPH generation, and biosynthesis of terpenoid backbone, fatty acid, sterol, and amino acids were allocated for leveraging biomass and lipid production through at least transcriptional control. This study revealed robust metabolic networks in the oleaginicity of A. oryzae governing glucose/xylose flux toward lipid biosynthesis that provides meaningful hints for further process developments of microbial lipid production using cellulosic sugar feedstocks.
