Filamentous fungi, such as Aspergillus, Trichoderma, and Penicillium species, are considered as unique cell factories for protein production due to the high efficiency of protein secretion and superior capability of post-translational modifications. Many species of filamentous fungi are generally regarded as safe (GRAS). Filamentous fungi have less extensive hyper-mannosylation of glycoproteins, which could be directly converted to mammalian type of glycoproteins with pharmaceutical potential. In addition, due to the metabolic diversity, filamentous fungi can efficiently utilize many types of monosaccharides including xylose, arabinose, and galactose. Filamentous fungi expression platforms have been successfully used for the production of industrial enzymes, therapeutic proteins, vaccines, and bioactive peptides. Their versatility and efficiency make them valuable tools in biotechnology and industrial bioprocessing.

To enhance the protein expression and secretion in filamentous fungi, enhancing the intracellular protein production by optimization of the transcription and/or the codon of the target protein, is an effective strategy. Genetic engineering strategies, including replacing original signal peptide with a more efficient one, fusion of heterologous protein to a naturally secreted one, regulation of UPR and ERAD, optimization of the intracellular transport process, construction of a protease-deficient strain, regulation of mycelium morphology, and optimization of the sterol regulatory element binding protein (SREBP).