Comparison of Different Strategies to Reduce Acetate Formation in Escherichia coli

E. coli cells produce acetate as an extracellular coproduct of aerobic cultures. Acetate is undesirable because it retards growth and inhibits protein formation. Most process designs or genetic modifications to minimize acetate formation aim at balancing growth rate and oxygen consumption. In this r...

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Bibliographic Details
Published in:Biotechnology progress 2007-09, Vol.23 (5), p.1053-1063
Main Authors: de Mey, Marjan, Lequeux, Gaspard J., Beauprez, Joeri J., Maertens, Jo, Van Horen, Ellen, Soetaert, Wim K., Vanrolleghem, Peter A., Vandamme, Erick J.
Format: Article
Language:English
Subjects:
Acetates - metabolism
Biological and medical sciences
Biotechnology
Carbon - metabolism
Computer Simulation
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Escherichia coli Proteins - genetics
Fundamental and applied biological sciences. Psychology
Genetic Enhancement - methods
Glucose - metabolism
Models, Biological
Mutation
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Summary:E. coli cells produce acetate as an extracellular coproduct of aerobic cultures. Acetate is undesirable because it retards growth and inhibits protein formation. Most process designs or genetic modifications to minimize acetate formation aim at balancing growth rate and oxygen consumption. In this research, three genetic approaches to reduce acetate formation were investigated: (1) direct reduction of the carbon flow to acetate (ackA‐pta, poxB knock‐out); (2) anticipation on the underlying metabolic and regulatory mechanisms that lead to acetate (constitutive ppc expression mutant); and (3) both (1) and (2). Initially, these mutants were compared to the wild‐type E. coli via batch cultures under aerobic conditions. Subsequently, these mutants were further characterized using metabolic flux analysis on continuous cultures. It is concluded that a combination of directly reducing the carbon flow to acetate and anticipating on the underlying metabolic and regulatory mechanism that lead to acetate, is the most promising approach to overcome acetate formation and improve recombinant protein production. These genetic modifications have no significant influence on the metabolism when growing the micro‐organisms under steady state at relatively low dilution rates (less than 0.4 h−1).
ISSN:8756-7938
1520-6033
DOI:10.1021/bp070170g