Engineering of Therapeutic Proteins Production in Escherichia coli

Mariusz      Kamionka

doi:10.2174/138920111794295693

Abstract

Low cost and simplicity of cultivating bacteria make the E. coli expression system a preferable choice for production of therapeutic proteins both on a lab scale and in industry. In addition straightforward recombinant DNA technology offers engineering tools to produce protein molecules with modified features. The lack of posttranslational modification mechanisms in bacterial cells such as glycosylation, proteolytic protein maturation or limited capacity for formation of disulfide bridges may, to a certain extent, be overcome with protein engineering. Protein engineering is also often employed to improve protein stability or to modulate its biological action. More sophisticated modifications may be achieved by genetic fusions of two proteins. This article presents a variety of examples of genetic engineering of therapeutic proteins. It emphasizes the importance of designing a construct without any unnecessary amino acid residues.

Keywords: Biopharmaceuticals, drug development, protein drugs, protein engineering, protein expression, therapeutic proteins, Escherichia coli, recombinant DNA technol-ogy, posttranslational modifica-tion, glycosylation, proteolytic protein, recombinant human insu-lin, gene transcription, conjugation process, amino acid residues, mono-clonal antibodies, eukaryotic expres-sion systems, glycans, interleukin-2 (IL-2), aldesleukin, Proleukin, Recom-binant human interferon- (rhIFN-), Recombinant human erythropoietin (rhEPO), darbepoetin alfa, anemia cases, lysine resi-dues, hydrophobic protein, electrostatic interac-tions, cysteine residues, N-glycosyl iodoacetamide, methionine cleavage, Disulfide Bridges, eukaryotic proteins, disulfide oxidoreductase (DsbA) protein, human growth hormone (hGH), teine residues, protein crystallization, keratino-cyte growth factor (KGF), dimerization process, lispro, insulin aspart, insulin glulisine, insulin detemir, serum albumin, Human deoxyribonuclease I, Interferon con-1, cytokine, GENETIC FUSIONS, Albinterferon -2b (alb-IFN), growth hormone, B-type natriuretic, granulocyte, immunogenic-ity, encepha-lopathies, methionine residue, filgrastim, ancestim, IL-1 receptor antagonist IL-1Ra, anakinra