Refolding and purification of Apo2l/TRAIL produced as inclusion bodies in high-cell-density cultures of recombinant Escherichia coli

Biotechnol Lett. 2003 Dec;25(24):2097-101. doi: 10.1023/b:bile.0000007072.56577.0c.

Abstract

As a new member of tumor necrosis factor (TNF) superfamily, TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) was produced mainly as inclusion bodies by recombinant Escherichia coli with a temperature-inducible expression system. High concentrations of both biomass (65 g dry cells l(-1)) and inactive TRAIL (4.8 g l(-1)) were obtained by applying a high-cell-density cultivation procedure. After the inclusion bodies were washed and solubilized. TRAIL refolded when at 1 mg ml(-1) by a simple pulse dilution method with a 35% yield. Renatured TRAIL was purified to electrophoretic homogeneity by one-step immobilized metal affinity chromatography. The purified TRAIL showed strong cytotoxicity activity against human pancreatic 1990 tumor cells, with ED50 about 1.6 microg ml(-1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor / drug effects
  • Cell Survival / drug effects
  • Chromatography, Affinity / methods
  • Dose-Response Relationship, Drug
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Humans
  • Inclusion Bodies / genetics
  • Inclusion Bodies / metabolism*
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / isolation & purification*
  • Membrane Glycoproteins / pharmacology
  • Pancreatic Neoplasms / physiopathology
  • Protein Engineering / methods
  • Protein Folding
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / isolation & purification*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha