A Novel Method for Producing Transgenic Enzymes and Peptides

Abstract

See report. We have successfully developed a novel a protein expression system based on the bacterium Raistonia eutropha. This system has been developed in our laboratory to overcome some of the shortcomings associated with recombinant protein expression in other bacteria (e.g. poor fermentation performance, inclusion body formation and proteolysis). High level expression of organophosphohydrolase (OPH), an enzyme prone to inclusion body formation in Escherichia coli has been demonstrated. A proteomics approach identified the promoter of the p(exp haP) gene as a strong, inducible promoter. By creating a translational fusion between the phaP promoter and oph gene and introducing this fusion into the chromosome, OPH titers of greater than 1 g/L were achieved in high cell density fermentations. Multiple copies of the P(exp phaP)::oph translational fusion were introduced into the chromosome to further increase expression. A proportional increase in OPH titer was found with increasing copy number. An OPH titer of approximately 4.3 g/L was measured in high cell density fermentation using a strain containing three copies of P(exp phaP)::oph) translational fusion This represents the highest titer reported to date for OPH (approximately 30 times greater than previously reported expression levels). Results have reported in two publications (Srinivasan et al. 2003; Srinivasan et al., 2002).

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Document Details

Document Type
Technical Report
Publication Date
Mar 04, 2004
Accession Number
ADA422909

Entities

People

  • Tillman U. Gerngross

Organizations

  • Dartmouth College

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Bacteria
  • Cells
  • Cellular Structures
  • Chemical Synthesis
  • Chemistry
  • Fungi
  • Liquid Chromatography
  • Medical Personnel
  • Microbiology
  • Organic Chemistry
  • Prokaryotes
  • Proteins
  • Proteomics
  • Recombinant Proteins

Fields of Study

  • Biology

Readers

  • Mathematics or Statistics
  • Microbial Pathology
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology