Expression of recombinant proteins with uniform N-termini

Methods Mol Biol. 2011:705:175-94. doi: 10.1007/978-1-61737-967-3_10.

Abstract

Heterologously expressed proteins in Escherichia coli may undergo unwanted N-terminal processing by methionine and proline aminopeptidases. To overcome this problem, we present a system where the gene of interest is cloned as a fusion to a self-splicing mini-intein. This fusion construct is expressed in an engineered E. coli strain from which the pepP gene coding for aminopeptidase P has been deleted. We describe a protocol using human cationic trypsinogen as an example to demonstrate that recombinant proteins produced in this expression system contain homogeneous, unprocessed N-termini.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminopeptidases / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / genetics
  • Gene Deletion
  • Humans
  • Inteins*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / biosynthesis*
  • Trypsinogen / biosynthesis*
  • Trypsinogen / genetics

Substances

  • Escherichia coli Proteins
  • Recombinant Fusion Proteins
  • Trypsinogen
  • Aminopeptidases
  • aminopeptidase P, E coli