Gaining insights about the mechanism of lignocellulose degradation by fungi is one of the pathbreaking discoveries for renewable-based biotechnology, specifically for the production of hydrolytic enzymes. Many detailed studies are available which evaluates fungal degradation when the expression levels of CAZyme reach its peak. However, the basic understanding of how fungi survive on lignocelluloses is still under the pipeline. This paper uses Aspergillus niger to explore its responses against six different substrates playing role in biofuel production. The responses to Miscanthus were compared with wheat straw, in isolation and in combination with ionic & hydrothermal feedstock pretreatment.  A metabolic model is mapped using a thorough evaluation of genome-wide transcriptome in combination with defined targeted transcripts and protein analyses. The exposure to different substrates showed enhancement in fatty acid oxidation and lipid metabolism transcripts. Strains with deletion of farA (ortholog of the fatty acid beta-oxidation transcriptional regulator) showed the reduced expression level of genes encoding lignocelluloses degradative CAZyme, indicating the role of beta-oxidation in mediating the adaptation to lignocelluloses. Activation of novel secondary metabolite gene clusters was noticed at the later life stages which are of great consideration due to their importance in synthesis of bioactive compounds. The entire study highlights that substrate composition and structure influence plays a critical role in mediating responses of fungi to lignocellulose. The study also shows the presence of different physiological stages in fungal responses which are mostly conserved across different substrates.

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