Production of recombinant human G-CSF from non-classical inclusion bodies in Escherichia coli

Braz J Microbiol. 2021 Jun;52(2):541-546. doi: 10.1007/s42770-020-00413-y. Epub 2021 Jan 22.

Abstract

Recombinant granulocyte colony-stimulating factor (G-CSF) protein produced in Escherichia coli has been widely used for the treatment of neutropenia induced by chemotherapy for decades. In E. coli cells, G-CSF is usually expressed as inactive inclusion bodies, which requires costly and inefficient denaturation and refolding steps to obtain the protein in its active form. However, following the findings of previous studies, we here successfully produced G-CSF in E. coli as non-classical inclusion bodies (ncIBs), which contained likely correctly folded protein. The ncIBs were easily dissolved in 0.2% N-lauroylsarcosine solution and then directly applied to a Ni-NTA affinity chromatography column to get G-CSF with high purity (> 90%). The obtained G-CSF was demonstrated to have a similar bioactivity with the well-known G-CSF containing product Neupogen (Amgen, Switzerland). Our finding clearly verified that the G-CSF production from ncIBs is a feasible approach to improve the yield and lower the cost of G-CSF manufacturing process.

Keywords: G-CSF; Granulocyte colony–stimulating factor; Non-classical inclusion body; Recombinant protein.

MeSH terms

  • Escherichia coli / chemistry
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Gene Expression*
  • Granulocyte Colony-Stimulating Factor / chemistry
  • Granulocyte Colony-Stimulating Factor / genetics*
  • Granulocyte Colony-Stimulating Factor / metabolism*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Humans
  • Inclusion Bodies / chemistry
  • Inclusion Bodies / genetics
  • Inclusion Bodies / metabolism*
  • Protein Folding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor