Controlled fed-batch by tracking the maximal culture capacity.

Area of Science:

• Biotechnology
• Biochemical Engineering
• Microbial Cultivation

Background:

• Fed-batch processes are standard in biotechnology to enhance product yield.
• Key challenges include managing overflow metabolism and toxic substrate accumulation.
• Current methods often rely on fixed feed rate profiles, potentially missing optimal control points.

Purpose of the Study:

• To develop and validate a dynamic fed-batch strategy for precise control of microbial culture physiology.
• To mitigate overflow metabolism and substrate toxicity in industrial bioprocesses.
• To enable real-time monitoring and adjustment of feeding strategies.

Main Methods:

• Implementing short, repetitive reductions in feed rate during fed-batch cultivation.
• Analyzing real-time, on-line culture responses to these feeding challenges.
• Applying the dynamic approach to production systems including Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli.

Main Results:

• The dynamic approach successfully identified and responded to potential overfeeding events.
• Minute amounts of overflow metabolites were depleted during feeding disturbances.
• The method proved effective in industrially relevant yeast and bacterial systems.

Conclusions:

• Dynamic fed-batch cultivation offers superior control over cell physiology compared to traditional methods.
• This strategy effectively prevents overflow metabolism and manages toxic substrates.
• The approach is robust and applicable to diverse microbial production platforms.