Continuous Bioprocessing for Recombinant Protein Production in <i>Bacillus subtilis</i>: Opportunities and Challenges

The Gram-positive bacterium Bacillus subtilis has long been used for industrial protein production owing to its well-characterised genetic background, capacity for high-density fermentation, and effective protein secretion. With the growing global demand for recombinant proteins across various sectors, there is an increasing need for more efficient and sustainable protein production methods. This review explores the application of continuous bioprocessing for recombinant protein production using B. subtilis, critically evaluating current technologies and discussing their potential for integration into streamlined, integrated biomanufacturing framework. We primarily focus on transgenic B. subtilis, however the solutions for continuous fermentation and protein isolation/purification are the same for both endogenous and heterologous (i.e., recombinant) proteins.