A secretory system for bacterial production of high-profile protein targets

Protein Sci. 2011 Mar;20(3):597-609. doi: 10.1002/pro.593.

Abstract

Escherichia coli represents a robust, inexpensive expression host for the production of recombinant proteins. However, one major limitation is that certain protein classes do not express well in a biologically relevant form using standard expression approaches in the cytoplasm of E. coli. To improve the usefulness of the E. coli expression platform we have investigated combinations of promoters and selected N-terminal fusion tags for the extracellular expression of human target proteins. A comparative study was conducted on 24 target proteins fused to outer membrane protein A (OmpA), outer membrane protein F (OmpF) and osmotically inducible protein Y (OsmY). Based on the results of this initial study, we carried out an extended expression screen employing the OsmY fusion and multiple constructs of a more diverse set of human proteins. Using this high-throughput compatible system, we clearly demonstrate that secreted biomedically relevant human proteins can be efficiently retrieved and purified from the growth medium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Secretion Systems / physiology*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Humans
  • Mass Spectrometry / methods
  • Periplasmic Binding Proteins / genetics
  • Periplasmic Binding Proteins / metabolism
  • Porins / genetics
  • Porins / metabolism
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / genetics

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Secretion Systems
  • Escherichia coli Proteins
  • OmpF protein
  • Periplasmic Binding Proteins
  • Porins
  • Recombinant Fusion Proteins
  • osmY protein, E coli
  • OMPA outer membrane proteins