Extraction of recombinant periplasmic proteins under industrially relevant process conditions: Selectivity and yield strongly depend on protein titer and methodology

Biotechnol Prog. 2020 Sep;36(5):e2999. doi: 10.1002/btpr.2999. Epub 2020 Apr 13.

Abstract

In this work, we attempted to identify a method for the selective extraction of periplasmic endogenously expressed proteins, which is applicable at an industrial scale. For this purpose, we used an expression model that allows coexpression of two fluorescent proteins, each of which is specifically targeted to either the cytoplasm or periplasm. We assessed a number of scalable lysis methods (high-pressure homogenization, osmotic shock procedures, extraction with ethylenediaminetetraacetic acid, and extraction with deoxycholate) for the ability to selectively extract periplasmic proteins rather than cytoplasmic proteins. Our main conclusion was that although we identified industrially scalable lysis conditions that significantly increased the starting purity for further purification, none of the tested conditions were selective for periplasmic protein over cytoplasmic protein. Furthermore, we demonstrated that efficient extraction of the expressed recombinant proteins was largely dependent on the overall protein concentration in the cell.

Keywords: Escherichia coli; chromoproteins; cytoplasmic protein extraction; detergent extraction; high-pressure homogenization; osmotic shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Fractionation
  • Detergents / chemistry*
  • Escherichia coli
  • Luminescent Proteins / chemistry
  • Luminescent Proteins / metabolism
  • Osmotic Pressure
  • Periplasmic Proteins* / analysis
  • Periplasmic Proteins* / isolation & purification
  • Periplasmic Proteins* / metabolism
  • Recombinant Proteins* / analysis
  • Recombinant Proteins* / isolation & purification
  • Recombinant Proteins* / metabolism

Substances

  • Detergents
  • Luminescent Proteins
  • Periplasmic Proteins
  • Recombinant Proteins