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Optimal nutrient feed policies for heterologous protein production


RecombinantEscherichia coli, which overproduce heterologous protein, redirect endogenous metabolic activity to that mediated by the recombinant expression vector. Consequently, cells may experience perturbations in the biosynthetic reaction network, including the amino acid biosynthesis pathways. These cells are characterized by decreased growth rate, decreased cell mass yield, and increased heterologous protein degradation. This study investigates the dynamics of chloramphenicol-acetyl-transferase (CAT) synthesis and degradation inE. coli JM105 grown on minimal media, and correlates the observed phenomena with induction strength. Coordinated amino acid feeding was shown to increase the heterologous protein yield. Rational design of nutrient feeding possibilities is explored.

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Correspondence to S. W. Harcum, D. M. Ramirez or W. E. Bentley.

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Harcum, S.W., Ramirez, D.M. & Bentley, W.E. Optimal nutrient feed policies for heterologous protein production. Appl Biochem Biotechnol 34, 161–173 (1992).

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Index Entries

  • Heterologous protein expression
  • stress response
  • protease activity
  • nutrient feed policies