In continuous fermentation, microorganisms are cultured to the logarithmic growth stage, where fresh liquid medium is continuously added to the fermenter at a certain speed, and fermentation liquid is simultaneously discharged at the same rate. This method not only reduces the time required for bioreactor cleaning and sterilization but also maintains constant cell concentration, pH, nutrient levels, and dissolved oxygen in the fermenter. As a result, microbial growth and metabolic activities remain vigorous, significantly improving fermentation efficiency and equipment utilization.
However, continuous fermentation typically operates over extended periods, requiring careful attention to equipment sealing and the sterility of air and liquid during selection. Prolonged fermentation also increases the risk of strain variation, making it difficult to maintain pure culture fermentation over time. Additionally, the continuous nature of the process complicates the separation of products into distinct batches for traceability.
Fed-batch fermentation is a method between batch and continuous fermentation, where fresh medium is added intermittently or continuously during the process to maintain a low substrate concentration in the system. This approach involves the slow addition of materials to the fermenter without continuous removal of fermentation liquid, meeting the needs of microbial growth and continuous product synthesis while alleviating substrate inhibition and improving target product yield. During the product synthesis stage, nutrient concentration must be controlled within a specific range to optimize product synthesis. Excess nutrients promote bacterial growth but inhibit product synthesis, while insufficient nutrients lead to bacterial aging and reduced synthesis capacity, both of which are detrimental to production.
Moreover, fed-batch fermentation is more advantageous than batch fermentation when the metabolite production rate or cell growth rate is significantly influenced by the concentration of a specific substrate component. Examples include: (1) high-density culture systems, (2) systems exhibiting the Crabtree effect, (3) systems subject to catabolite repression, and (4) systems utilizing auxotrophic mutants.