Heterologous Protein Production in Filamentous Fungi
Summary
Filamentous fungi have emerged as versatile cell factories for the manufacture of proteins that do not originate from the host organism. Their extensive secretion pathways, capacity for post-translational modification and high yields under industrial fermentation conditions make them highly attractive for biotechnological applications. Central to heterologous protein production is the integration of foreign genes into fungal genomes, coupled with the deployment of strong or inducible promoters, optimised signal peptides to direct secretion and host-specific codon usage for efficient translation. Challenges include the tendency of non-fungal proteins to misfold in the endoplasmic reticulum, leading to secretion stress, proteolytic degradation and altered glycosylation patterns. Recent advances in genome editing, high-throughput screening and process engineering have addressed these bottlenecks by tailoring the unfolded protein response, disrupting protease genes, engineering glycosylation pathways and refining culture media. Successful examples span enzymes for biomass conversion, therapeutic peptides and food-grade proteins, illustrating the global significance of filamentous fungi as heterologous platforms.
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Heterologous Protein Production in Filamentous Fungi publication trend
The graph below shows the total number of articles in heterologous protein production in filamentous fungi across all publications each year (not limited to Nature Index journals).
Technical terms
Heterologous protein: A protein expressed in a host organism from a foreign gene.
Filamentous fungi: Multicellular fungi that grow as branching hyphae and form a mycelial network.
Promoter: A DNA sequence that controls the initiation and level of gene transcription.
Signal peptide: A short amino-terminal sequence that directs nascent proteins into the secretory pathway.
Unfolded protein response: A cellular stress response activated by accumulation of misfolded proteins in the endoplasmic reticulum.
Codon optimisation: Modification of gene sequence to match the preferred codon usage of the host organism for efficient translation.
References
- Heterologous protein production in filamentous fungi. Applied Microbiology and Biotechnology (2023).
- Exploration of the Strategy for Improving the Expression of Heterologous Sweet Protein Monellin in Aspergillus niger. Journal of Fungi (2023).
- Fungal Cell Factories for Efficient and Sustainable Production of Proteins and Peptides. Microorganisms (2022).
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