Innovations in process engineering approaches for enhanced bacteriocin production

Bacteriocins are ribosomally synthesized antimicrobial peptides produced by various classes of bacteria, exhibiting broad-spectrum activity that makes them promising candidates for applications in food preservation and medicine. Their inherent stability under extreme pH, temperature, and salinity conditions further supports their functional versatility. However, the widespread industrial application of bacteriocins remains constrained by the low titres typically achieved during fermentation. Despite extensive efforts to optimize production using batch and fed-batch fermentation strategies, the resulting titres remain inadequate for economically viable large-scale manufacturing. This review aims to provide a comprehensive overview of novel process strategies developed over the past two decades to enhance bacteriocin yields during fermentation. One of the primary challenges is the inhibition of microbial growth due to the accumulation of lactic acid or the bacteriocin itself during production. To address this, in situ product removal techniques-such as co-cultivation with lactic acid-consuming microorganisms, in situ adsorption, filtration, and foam fractionation-have been explored, yielding notable improvements in bacteriocin titres. Additionally, stress-induced production strategies involving biological (e.g., co-culture with competing microbes), chemical (e.g., salinity and pH stress), and physical (e.g., agitation, temperature, and aeration stress) stimuli have also demonstrated success in enhancing bacteriocin synthesis. This review underscores the importance of these innovative fermentation approaches and highlights the need for further research focused on scaling up such processes. Advancing these strategies is critical to realizing the full potential of bacteriocins in food safety, antimicrobial therapy, and broader biomedical applications. One-sentence summary This review provides a comprehensive view of the novel fermentation strategies developed in the last two decades to overcome low bacteriocin titres during fermentation such as in situ lactate removal, in situ bacteriocin removal, and stress-led induction.