Genetic Engineering of Filamentous Fungi for Efficient Protein Expression and Secretion

Summary

This research reviews how scientists can genetically modify fungi to produce proteins more efficiently for industrial and medical uses. Fungi are excellent natural protein factories that can be improved through various genetic modifications. This matters because: • More efficient protein production could lead to cheaper medicines and industrial enzymes • Better understanding of fungal genetics helps develop new biotechnology applications • Improved protein production methods can be more environmentally sustainable • These advances may lead to new therapeutic proteins and industrial products • The research helps make biological manufacturing processes more cost-effective

Background

Filamentous fungi are powerful and efficient cell factories for protein production at industrial scale, producing over half of commercially available proteins. They are generally regarded as safe (GRAS) and exhibit superior protein secretory capability compared to other organisms. Unlike prokaryotes, filamentous fungi have mature systems for post-translational processing like glycosylation and can efficiently utilize various monosaccharides.

Objective

This review aims to summarize current genetic engineering strategies for enhancing protein expression and secretion in filamentous fungi, focusing on approaches beyond traditional fermentation optimization and random mutagenesis. It also discusses the potential of genome engineering for further improvements.

Results

Multiple genetic engineering strategies showed success in improving protein expression and secretion. Signal peptide replacement increased α-galactosidase activity by 9-fold. Fusion proteins showed 2-fold increases in production. UPR/ERAD regulation led to 1.5-1.8 fold improvements. Transport optimization achieved 2.2-fold increases. Protease-deficient strains showed 5-fold higher cellulase production. Mycelium morphology regulation increased glucoamylase secretion 4-fold.

Conclusion

While current genetic engineering strategies have significantly improved target protein production, they mainly focus on single genes or pathways. Future applications of genome engineering technologies, coupled with high-throughput screening methods, show great potential for further enhancing protein expression and secretion in filamentous fungi.
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