US EPA

1048510 

Journal Article 

Controlled fed-batch by tracking the maximal culture capacity 

Henes, B; Sonnleitner, B 

2007 

Yes 

Journal of Biotechnology
ISSN: 0168-1656
EISSN: 1873-4863 

132 

2 

118-126 

English 

17573139 

10.1016/j.jbiotec.2007.04.021 

WOS:000251116700004 

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). 

real-time feed control; fed-batch; hypothesis testing; comparison of variance; controller and sensitivity testing; exploration of strategies