Morphological differentiation and its application in industrial filamentous fungi

Filamentous fungi are essential ecosystem members and major platforms for industrial biomanufacturing, where their morphological differentiation strongly influences broth rheology, mass/oxygen transfer, secretion efficiency, stress tolerance, and ultimately productivity. However, the intricate network in which process-specific cues are sensed and integrated to reprogram the endogenous developmental pathways remains incompletely understood, limiting rational morphology engineering of the industrial filamentous fungi. This review summarizes recent advances in the regulation of morphological differentiation of filamentous fungi, integrating internal and external signaling along with molecular control of spore germination, polarity establishment, hyphal extension/branching, and cell wall-plasma membrane homeostasis. We discuss how distinct morphologies affect performance in submerged and solid-state fermentation, and we overview the practical control strategies including inoculation design, environmental and hydrodynamic optimization, microparticle-enhanced cultivation, and genetic reprogramming. Finally, we highlight emerging monitoring approaches and recent progress in machine learning and modeling within AI-enabled biomanufacturing, proposing an integrated gene-morphology-function-titer perspective for next-generation fungal cell factories.