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.
Advantages for Protein Expression in Filamentous fungi
High Protein Secretion Capacity
Filamentous fungi have a robust protein secretion system, allowing efficient extracellular production and accumulation of recombinant proteins. They naturally secrete a wide range of hydrolytic enzymes, making them well-suited for industrial enzymes production.
Post-translational Modifications
Filamentous fungi have the capability to perform various post-translational modifications, including glycosylation, proteolytic processing, and disulfide bond formation. These modifications can enhance protein stability, activity, and functionality, particularly for complex therapeutic proteins.
Scalability
Filamentous fungi can be grown at large scales using inexpensive substrates, such as agricultural residues, lignocellulosic biomass, or by-products from various industries. This makes them economically favorable for industrial production.
Genetic Tractability
Many filamentous fungi have well-established genetic tools and techniques for strain improvement, gene manipulation, and genetic engineering. This enables the optimization of strains for higher protein yields and better product quality.
Wide Substrate Utilization
Filamentous fungi can utilize a broad range of carbon sources, including complex polysaccharides, lignocellulosic materials, and various industrial waste streams. This versatility allows for cost-effective production using diverse feedstocks.
Efficient Strategies for Protein Expression and Secretion in Filamentous fungi
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).
Options for Filamentous fungi Expression System
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Services
Design and construct expressing vector
Gene synthesis and codon optimization
Screening of transformants
Harmonize cultivating conditions
Production in accordance with GMP regulations
Figure 1 Standard workflow for heterologous expression in filamentous fungi. (COLIN J. B. HARVEY, et al. 2018)
Our Strengths
Multiple and well-established genetic engineered filamentous fungi expressing strains A series of alternative promoters that meet different requirements Manifold selectable markers High yield with fabulous bioactivity
Creative Biogene is a professional protein expression development and service company with decades of experience. Our team of outstanding scientists from around the world, focusing on filamentous fungi research, aims to provide you with the best strategies and services.
If you are interested in our services, please contact us for more details.
References
Qin Wang, et al. Genetic Engineering of Filamentous Fungi for Efficient Protein Expression and Secretion. Front. Bioeng. Biotechnol. 2020.
COLIN J. B. HARVEY, et al. HEx: A heterologous expression platform for the discovery of fungal natural products. SCIENCE ADVANCES. 2018.
Figure 1 Standard workflow for heterologous expression in filamentous fungi. (COLIN J. B. HARVEY, et al. 2018)