Integrating T7 RNA Polymerase and Its Cognate Transcriptional Units for a Host-Independent and Stable Expression System in Single Plasmid

ACS Synth Biol. 2018 May 18;7(5):1424-1435. doi: 10.1021/acssynbio.8b00055. Epub 2018 Apr 19.

Abstract

Metabolic engineering and synthetic biology usually require universal expression systems for stable and efficient gene expression in various organisms. In this study, a host-independent and stable T7 expression system had been developed by integrating T7 RNA polymerase and its cognate transcriptional units in single plasmid. The expression of T7 RNA polymerase was restricted below its lethal threshold using a T7 RNA polymerase antisense gene cassette, which allowed long periods of cultivation and protein production. In addition, by designing ribosome binding sites, we further tuned the expression capacity of this novel T7 system within a wide range. This host-independent expression system efficiently expressed genes in five different Gram-negative strains and one Gram-positive strain and was also shown to be applicable in a real industrial d- p-hydroxyphenylglycine production system.

Keywords: T7 RNA polymerase; antisense RNA; host-independent expression system; single plasmid; stable expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antisense Elements (Genetics)
  • Binding Sites
  • Corynebacterium glutamicum / genetics
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism
  • Gene Expression Regulation, Bacterial
  • Glycine / analogs & derivatives*
  • Glycine / biosynthesis
  • Gram-Negative Bacteria / genetics
  • Metabolic Engineering / methods*
  • Microorganisms, Genetically-Modified
  • Plasmids / genetics*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Ribosomes / metabolism
  • Sinorhizobium / genetics
  • Transcription, Genetic
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • Antisense Elements (Genetics)
  • Recombinant Proteins
  • Viral Proteins
  • 4-hydroxyphenylglycine
  • bacteriophage T7 RNA polymerase
  • DNA-Directed RNA Polymerases
  • Glycine