Expression of tetanus toxin fragment C

Methods Mol Biol. 1998:103:193-208. doi: 10.1385/0-89603-421-6:193.

Abstract

1. The yield of fragment C was only modestly affected by Mut phenotype, and the site and type of integration event. 2. Fragment C accumulation was closely correlated with gene dosage and maximal expression levels required high gene copy number. 3. Yields were greatly increased in controlled fermenters, compared to shake-flasks, owing to the high cell density achieved and to an increased efficiency of induction (2.5- to 10-fold). 4. In fermenter inductions of a 14-copy strain, fragment C accumulated to 27% of total protein, giving an estimated yield of 12 g/L. 5. Considerable clonal variation in the level of expression occurred with transplacement transformants, and this was owing to a diversity of different integration events and to differences in gene copy number. 6. These multicopy transplacement events occur by in vivo circularization of transforming DNA fragments followed by repeated single-crossover integration. This is presumably a general phenomenon, such that it should be possible to obtain multicopy integrants from all P. pastoris transplacement transformations.

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Chromosomes, Fungal
  • Cloning, Molecular / methods
  • Clostridium tetani / genetics
  • Electrophoresis, Polyacrylamide Gel / methods
  • Fermentation
  • Genetic Vectors
  • Indicators and Reagents
  • Neuromuscular Blocking Agents
  • Peptide Fragments / biosynthesis*
  • Peptide Fragments / genetics
  • Peptide Fragments / isolation & purification
  • Pichia / genetics
  • Pichia / growth & development
  • Plasmids
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Tetanus Toxin / biosynthesis*
  • Tetanus Toxin / genetics
  • Tetanus Toxin / isolation & purification
  • Transformation, Genetic

Substances

  • Indicators and Reagents
  • Neuromuscular Blocking Agents
  • Peptide Fragments
  • Recombinant Proteins
  • Tetanus Toxin
  • tetanus toxin fragment C
  • Alcohol Oxidoreductases
  • alcohol oxidase