Morphological Engineering of Filamentous Fungi: Research Progress and Perspectives

the food, textile, medical, and chemical industries and have great commercial application value [4,5].For example, filamentous fungi, especially Ascomycetes and Basidiomycetes, are known to produce an extraordinary range of colors, including several chemical classes of pigments, such as melanins, azaphilones, flavins, phenazines, and quinines [6].Compared to other conventional sources, industry is more focused on filamentous fungi, which can be easily grown in the laboratory and provide the possibility of large-scale production [7].Filamentous fungi can secrete a wide variety and large amounts of enzymes, including glycosylases, proteases, phytases, pectinases, and peroxidases [8-10], which can degrade polymers in organic wastes, such as (hemi)cellulose and starch, into small molecules as energy and carbon sources.Thus, filamentous fungi also play an important role in nature by degrading organic wastes [11,12].The enormous secretion capacity of fungi has already been used by industry for decades to produce organic acids and polymers, represented by citric acid, polylactic acid, gluconic acid, itaconic acid and lactic acid, as potential alternatives to petroleum-based plastics or raw materials [13].Of these, citric acid has been commercially produced using Aspergillus niger for almost a century, generating significant economic value [14].In addition, filamentous fungi are productive strains of some important antibiotics, such as penicillin [15].Thus, filamentous fungi have wide applications in the food, chemical, agriculture, and pharmaceutical industries, and research on them plays a catalytic role in the emerging global bio-economy, circular economy, and healthcare.Despite the obvious advantages of working with filamentous fungi, it can sometimes seem difficult to obtain higher production levels.In traditional food fermentation processes, such as wine making, filamentous fungi tend to carry out their metabolic activities in the form of mycelia [16].In large-scale industrial production, submerged fermentation is typically used to efficiently produce large quantities of product using aerated-stirred bioreactors [17].However, in submerged fermentation, filamentous fungi are often associated with highly non-Newtonian properties and variations in fungal morphology.Bacterial and yeast growth can be easily described by the duplication of single cells, whereas filamentous fungi undergo a complex morphological evolution from conidia to hyphae to dispersed mycelia or distinct particles [18].Variations in fungal morphology are not only difficult to detect and control, but are often accompanied by changes in the rheological, mass transfer, and mixing properties of the fermentation broth [19].This makes the fermentation process complex and difficult to control, which in turn affects the synthesis of the target product and the efficiency of the fermentation process.The dispersed hyphae increase the viscosity of the medium, which affects mass transfer, and nutrient distribution is extremely uneven.The hyphae will wrap around the impellers of the fermentation tank, causing clogging and diffusion into the sampling and overflow lines [20].However, compared to other microorganisms, apart from the greater Filamentous fungi are important cell factories for the production of high-value enzymes and chemicals for the food, chemical, and pharmaceutical industries.Under submerged fermentation, filamentous fungi exhibit diverse fungal morphologies that are influenced by environmental factors, which in turn affect the rheological properties and mass transfer of the fermentation system, and ultimately the synthesis of products.In this review, we first summarize the mechanisms of mycelial morphogenesis and then provide an overview of current developments in methods and strategies for morphological regulation, including physicochemical and metabolic engineering approaches.We also anticipate that rapid developments in synthetic biology and genetic manipulation tools will accelerate morphological engineering in the future.