A Probing Feeding Strategy for E. coli Cultivations

Författare

Jan Peter Axelsson
Mats Åkesson
Per Hagander

Summary, in English

Accumulation of acetate tends to reduce growth and recombinant protein production in E. coli cultivations. Formation of acetate can be avoided by a proper substrate feeding strategy, but most strategies require considerable process knowledge to work well. A feedback strategy is presented that requires minimal a priori information. The key idea is to exploit a characteristic change in the cell metabolism at the onset of acetate formation. By superimposing short pulses in the substrate feed rate, on-line detection of acetate formation can be made using a standard dissolved oxygen sensor. A simple feedback algorithm is then used to adjust the feed rate to avoid acetate formation while maintaining a high growth rate. The strategy was used in fed-batch cultivations of recombinant E. coli. Acetate accumulation was avoided and a good production of recombinant protein could be achieved at the first attempt for each genetic construction.

Avdelning/ar