Proteins are essential molecules used in medicines, vaccines, diagnostics, food processing, and many industrial applications. Today, many of these proteins are made using bacteria, which act like microscopic factories. Bacteria are preferred because they grow quickly, cost less to maintain, and are easier to genetically modify than plants or animal cells. However, producing large amounts of high-quality, functional proteins in bacteria—especially proteins that need to be released outside the cell—is still a major scientific challenge.
This review explains how researchers are overcoming these limitations by improving heterologous protein production, meaning proteins made by bacteria that originally come from other organisms, including humans. It compares commonly used bacterial hosts such as Escherichia coli, Bacillus subtilis, Bacillus licheniformis, and Brevibacillus choshinensis, highlighting their strengths and weaknesses for protein production.
A major focus of the paper is on protein secretion pathways, the natural systems bacteria use to move proteins across their cell membranes. These include the Sec pathway, which exports unfolded proteins, the Tat pathway, which transports fully folded proteins, and ABC transporters, which use energy to move proteins outside the cell. By engineering these pathways, scientists can help bacteria release proteins directly into the culture medium, making purification easier and cheaper.
The review also discusses modern strategies to improve protein yield and quality, such as optimizing DNA sequences to match bacterial preferences, engineering signal peptides that guide proteins to secretion pathways, using fusion proteins to improve folding and stability, and modifying bacterial strains to reduce protein breakdown. Advanced tools like synthetic biology and CRISPR/Cas9-based gene editing are highlighted as powerful methods to fine-tune bacterial systems for higher productivity.
Overall, the article shows that combining genetic engineering, secretion pathway optimization, and improved bacterial host design can greatly enhance the large-scale production of valuable therapeutic and industrial proteins, paving the way for more efficient and affordable biomanufacturing.
Fill publication: Devtulya Chander, Diksha Koul, Arushe Tickoo, Asha Chaubey, Advancing recombinant protein production by bacteria: strategies and challenges in heterologous systems, Current Research in Biotechnology, Volume 10, 2025, 100342, https://doi.org/10.1016/j.crbiot.2025.100342.