Advancing recombinant protein production by bacteria: strategies and challenges in heterologous systems

Le résumé fourni par la source

• Gram-positive bacteria like Brevibacillus , Bacillus subtilis and lactobacillus are emerging as efficient hosts for heterologus recombinant protein production due to their robust secretion systems. These secretion pathways allow expression of active soluble proteins in case of non-soluble complex proteins. • Sec, Tat, ABC transporter pathways play important roles in secretion of heterologous protein and therefore can be tailored for expression of proteins. • Advancements in genetic engineering, including CRISPR/Cas9n, enhance secretion efficiency, improving yields for therapeutic proteins and industrial enzymes. Recombinant protein production in bacteria is pivotal in industrial biotechnology, which enables scalable, cost-effective, and efficient synthesis of therapeutic proteins and enzymes. Present review explores key bacterial hostsincluding Escherichia coli , Bacillus subtilis , Bacillus licheniformis , and Brevibacillus choshinensis and more with an emphasis on extracellular heterologous protein production. Herein,we focus on secretion pathways such as Sec, Twin-arginine translocation (Tat) pathway, and ATP Binding Cassette (ABC) transporter systems, which govern protein export across membranes. The molecular strategiesranging from promoter optimization and codon adaptation to signal peptide engineering, strain modification, as well as protein fusion techniques have been highlighted that lead to improved secretion efficiency and product yields. Comparative insights into Gram-positive and Gram-negative systems, along with case studies, as well as importance of tailored approaches for different hosts and proteins have been reviewed. The review further discusses the growing relevance of CRISPR/Cas9n-based genetic interventions and the role of microbial physiology in facilitating optimized protein folding and transport. Overall, the integration of synthetic biology, secretion engineering, and host optimization offers promising avenues for advancing the extracellular production of high-value recombinant proteins.

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