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On‐line detection of acetate formation in Escherichia coli cultures using dissolved oxygen responses to feed transients
Author(s) -
Åkesson Mats,
Karlsson Eva Nordberg,
Hagander Per,
Axelsson Jan Peter,
Tocaj Anita
Publication year - 1999
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/(sici)1097-0290(19990905)64:5<590::aid-bit9>3.0.co;2-t
Subject(s) - substrate (aquarium) , chemistry , oxygen , escherichia coli , recombinant dna , chromatography , biochemistry , biology , organic chemistry , ecology , gene
Recombinant protein production in Escherichia coli 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. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 590–598, 1999.