Heterologous Protein Production in Bacillus-Based Expression Systems

Bacillus species, notably Bacillus subtilis, are prized hosts for the production of heterologous proteins thanks to their innate capacity for high-level secretion and generally recognised safety status. Expression constructs typically harness strong promoters, optimised ribosome binding sites and carefully selected signal peptides to direct nascent polypeptides into the Sec or Tat secretion pathways. Once translocated across the cytoplasmic membrane, folding factors and chaperones assist in attaining functional conformation before proteins reach the extracellular milieu. Common bottlenecks include secretion stress responses, proteolytic degradation by endogenous proteases and limits in folding capacity. Recent strategies to overcome these barriers employ genome engineering to delete unwanted proteases, overexpress quality-control factors, employ combinatorial signal peptide libraries and fine-tune transcriptional and translational control elements. Scale-up in bioreactors has translated many of these advances into industrially relevant yields, underpinning applications in enzyme manufacture, pharmaceuticals and biomanufacturing of complex proteins.

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Heterologous Protein Production in Bacillus-Based Expression Systems publication trend

The graph below shows the total number of articles in heterologous protein production in bacillus-based expression systems across all publications each year (not limited to Nature Index journals).

Technical terms

Heterologous protein production: Expression of a foreign protein in a host organism.

Signal peptide: Short amino-terminal sequence that directs a protein to the secretion machinery.

Sec pathway: Primary route for translocating unfolded proteins across the cytoplasmic membrane.

Promoter: DNA sequence that recruits RNA polymerase to initiate gene transcription.

Ribosome binding site (RBS): RNA sequence upstream of the start codon that aligns the ribosome for translation.

Chaperone: Protein that assists folding and prevents aggregation of nascent proteins.

References

1. The Construction of an Environmentally Friendly Super-Secreting Strain of Bacillus subtilis through Systematic Modulation of Its Secretory Pathway Using the CRISPR-Cas9 System. International Journal of Molecular Sciences (2024).
2. Enhanced extracellular production of raw starch-degrading α-amylase in Bacillus subtilis through expression regulatory element modification and fermentation optimization. Microbial Cell Factories (2023).
3. Post-translational secretion stress regulation in Bacillus subtilis is controlled by intra- and extracellular proteases. New Biotechnology (2023).