The filamentous fungus Aspergillus niger serves as an efficient microbial cell factory for producing enzymes, organic acids, and antibiotics. Its complex morphology in submerged cultivation significantly impacts production performance, though controlling this morphology has been challenging. Understanding the link between morphological shape and production characteristics is crucial. Comprehensive strategies that combine systems-wide analysis with process-driven engineering of the bioreactor environment are essential for optimizing production processes. This approach has been successfully applied to recombinant protein production in A. niger. By incorporating talc or alumina micro particles into the culture, researchers were able to precisely control the fungus's morphology, enhancing enzyme production in various recombinant strains. Additionally, targeted engineering of A. niger into high-producing bio-pellet forms using titanate micro particles was demonstrated. This strategy, coupled with model-based medium design and efficient fed-batch strategies, optimized the production of fructofuranosidase, a valuable biocatalyst for neo-sugar in the food and pharmaceutical industries, achieving an enzyme titre of 2,800 U/mL—over tenfold improvement. The enzyme facilitated the biosynthesis of 450 g/L of neo-sugar, such as kestose and nystose, which have significant commercial potential. Complementary systems biotechnology analyses of
