Controlled Fed-batch by Tracking the Maximal Culture Capacity

Fed-batch processes are well established in the biotech industry. The major reason to apply this technique is to avoid overflow metabolism and/or accumulation of toxic substrates. The basic idea of this approach is to control the physiological state of the culture, rather than just the typically exponential feed rate profile, by challenging a fed-batch cultivation repetitive in useful time intervals. The feed rate is reduced for a short period and culture responses are analysed in real time and on-line. Thus it is possible to get a positive response at the earliest detectable point of potential overfeeding. During the disturbance minute amounts of overflow metabolites will deplete simultaneously. This highly dynamic approach was applied successfully to industrially relevant production systems such as yeasts (Saccharomyces cerevisiae, Pichia pastoris) and bacteria (Escherichia coli).