On-line Detection of Acetate Formation in Escherichia coli Cultures using Dissolved Oxygen Responses to Feed Transients

Summary, in English

Recombinant protein production in <i>Escherichia coli</i> can be significantly reduced by acetate accumulation. It is demonstrated that acetate production can be detected on-line with a standard dissolved oxygen sensor by superimposing short pulses to the substrate feed rate. Assuming that acetate formation is linked to a respiratory limitation, a model for dissolved oxygen responses to transients in substrate feed rate is derived. The model predicts a clear change in the character of the transient response when acetate formation starts. The predicted effect was verified in fed-batch cultivations of E. coli TOPP1 and E. coli BL21(DE3), both before and after induction of recombinant protein production. It was also observed that the critical specific glucose uptake rate, at which acetate formation starts, was significantly decreased after induction. On-line detection of acetate formation with a standard sensor opens up new possibilities for feedback control of substrate feeding.

• Author: Mats Åkesson; Eva Nordberg Karlsson; Per Hagander; Jan Peter Axelsson; Anita Tocaj
• Department/s: Biotechnology; Department of Automatic Control
• Publishing year: 1999
• Language: English
• Pages: 590-598
• Publication/Series: Biotechnology and Bioengineering
• Volume: 64
• Issue: 5
• Links: http://dx.doi.org/10.1002/(SICI)1097-0290(19990905)64:5<590::AID-BIT9>3.0.CO;2-T/abstract
• Document type: Journal article
• Publisher: John Wiley & Sons Inc.
• Topic: Industrial Biotechnology; Control Engineering
• Keywords: on-line detection; acetate; \emph{Escherichia coli}; dissolved oxygen; transients; mathematical model
• Status: Published
• ISBN/ISSN/Other: ISSN: 1097-0290