A Probing Feeding Strategy for E. coli Cultivations

• 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.

Subject headings

TEKNIK OCH TEKNOLOGIER  -- Elektroteknik och elektronik -- Reglerteknik (hsv//swe)

ENGINEERING AND TECHNOLOGY  -- Electrical Engineering, Electronic Engineering, Information Engineering -- Control Engineering (hsv//eng)

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