Protein secretion systems in microbial and mammalian cells

Area of Science:

• Biotechnology
• Molecular Biology
• Protein Engineering

Background:

• Secretion is advantageous for proteins needing posttranslational modifications (folding, disulfide bonds, glycosylation).
• Secreted protein recovery is simplified as cells remain intact, and the product is concentrated in the medium.
• Heterologous protein production and secretion are feasible with current biotechnological methods.

Purpose of the Study:

• To review the state-of-the-art in heterologous protein secretion.
• To highlight the advantages of secretion for protein production and recovery.
• To discuss the selection of appropriate host systems for protein secretion based on protein characteristics and economic factors.

Main Methods:

• Review of current literature and established methods for protein secretion.
• Analysis of different microbial and mammalian host systems for protein production.
• Case studies illustrating the choice of host systems for specific protein types (e.g., therapeutics vs. industrial proteins).

Main Results:

• Current methods achieve commercially relevant secretion levels from diverse hosts including E. coli, B. subtilis, S. cerevisiae, Aspergilli, and mammalian cells.
• Specific host systems demonstrate advantages for different protein classes: mammalian cells for high-value therapeutics (e.g., plasminogen activators), and yeast/Aspergillus for economical industrial proteins (e.g., calf prochymosin).
• While efficiency improvements are ongoing, existing systems provide viable options for secreted protein production.

Conclusions:

• Protein secretion offers a powerful strategy for producing proteins requiring complex modifications and simplifies downstream processing.
• The selection of an optimal host system is protein-specific, balancing modification requirements, production scale, and economic considerations.
• The diversity of posttranslational modifications suggests that multiple secretion systems will coexist and be optimized for various applications in the foreseeable future.