A novel bacterial expression method with optimized parameters for very high yield production of triple-labeled proteins

Methods Mol Biol. 2012:831:1-18. doi: 10.1007/978-1-61779-480-3_1.

Abstract

The Gram-negative bacterium Escherichia coli offer a means for rapid, high-yield, and economical production of recombinant proteins. However, when preparing protein samples for NMR, high-level production of functional isotopically labeled proteins can be quite challenging. This is especially true for the preparation of triple-labeled protein samples in D(2)O ((2)H/(13)C/(15)N). The large expense and time-consuming nature of triple-labeled protein production for NMR led us to revisit the current bacterial protein expression protocols. Our goal was to develop an efficient bacterial expression method for very high-level production of triple-labeled proteins that could be routinely utilized in every NMR lab without changing expression vectors or requiring fermentation. We developed a novel high cell-density IPTG-induction bacterial expression method that combines tightly controlled traditional IPTG-induction expression with the high cell-density of auto-induction expression. In addition, we optimize several key experimental protocols and parameters to ensure that our new high cell-density bacterial expression method routinely produces 14-25 mg of triple-labeled proteins and 15-35 mg of unlabeled proteins from 50-mL bacterial cell cultures.

MeSH terms

  • Bioreactors*
  • Carbon Isotopes
  • Deuterium
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / metabolism*
  • Isopropyl Thiogalactoside
  • Isotope Labeling / methods*
  • Nitrogen Isotopes
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Recombinant Proteins / biosynthesis*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism

Substances

  • Carbon Isotopes
  • Nitrogen Isotopes
  • Recombinant Proteins
  • Isopropyl Thiogalactoside
  • Deuterium