Renaturation and purification of bone morphogenetic protein-2 produced as inclusion bodies in high-cell-density cultures of recombinant Escherichia coli

J Biotechnol. 2002 Mar 28;94(2):185-94. doi: 10.1016/s0168-1656(01)00425-4.

Abstract

Eschericha coli was genetically engineered to produce recombinant human bone morphogenetic protein-2 (rhBMP-2) in a non-active aggregated form using a temperature-inducible expression system. High concentrations of both biomass (75 g cell dry weight per liter of culture broth) and inactive rhBMP-2 (8.6 gl(-1)) were obtained by applying a high-cell-density cultivation procedure. After washing and solubilizing the inclusion bodies, rhBMP-2 was refolded and dimerized at concentrations up to 100 mgl(-1) by means of a simple dilution method with yields exceeding 50%. Finally, a one-step purification procedure based on affinity chromatography was implemented to isolate the rhBMP-2 dimer. With the established renaturation and purification protocols, yields of more than 10 mg rhBMP-2 dimer per gram cell dry weight were obtained corresponding to 750 mg rhBMP-2 dimer per liter of culture broth. The purified rhBMP-2 dimer showed biological activity equivalent to CHO produced rhBMP-2 as tested by the induction of alkaline phosphatase activity in C2C12 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / isolation & purification*
  • Bone Morphogenetic Proteins / metabolism
  • Culture Media
  • Dimerization
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development
  • Genetic Engineering
  • Inclusion Bodies / metabolism*
  • Protein Conformation
  • Protein Folding
  • Protein Renaturation
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Transforming Growth Factor beta*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Culture Media
  • Recombinant Proteins
  • Transforming Growth Factor beta