Lactose fed-batch overexpression of recombinant metalloproteins in Escherichia coli BL21 (DE3): process control yielding high levels of metal-incorporated, soluble protein

Protein Expr Purif. 1995 Oct;6(5):646-54. doi: 10.1006/prep.1995.1085.

Abstract

A method for producing recombinant proteins in pilot scale fermentation equipment using a glucose fed-batch initial growth, followed by a midlog phase feeding of a glucose and lactose mixture is described. Using the host strain Escherichia coli BL21(DE3), the diiron protein stearoyl-acyl carrier protein delta 9 desaturase has been overexpressed at a biomass level of up to 12 g x liter-1 dry cell weight, representing a 12-fold increase in volumetric productivity relative to that obtained from batch fermentations. Under these conditions, a maximum of 36% of the total cellular protein accumulates as the desaturase polypeptide. A correlation between the slowed growth rate of the fed-batch culture, a continued, albeit slower, exponential growth under inducing conditions, and a favorable partitioning between formation of the soluble holoprotein and inclusion bodies is reported. This correlation suggests that fed-batch techniques can be used to beneficially influence rate-limiting processes in the maturation of overexpressed proteins, such as metal uptake and incorporation proposed here. By using cells produced from the fed-batch method, the iron-containing, soluble desaturase can be purified in a yield of up to 66 mg x g-1 dry cell weight (approximately 500 mg x liter-1 culture), representing a three to fivefold increase in the yield relative to that obtained from batch fermentations. In addition, these methods are suitable for the production of the Anabena 7120 vegetative [2Fe 2S] ferredoxin in E. coli BL21(DE3) pLysS, a host strain used for the overexpression of toxic proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division
  • Cells, Cultured
  • Culture Media
  • Escherichia coli / cytology
  • Escherichia coli / metabolism*
  • Fermentation
  • Glucose / chemistry
  • Glucose / metabolism
  • Iron / metabolism
  • Lactose / metabolism*
  • Pilot Projects
  • Plasmids
  • Recombinant Proteins / biosynthesis
  • Stearoyl-CoA Desaturase / biosynthesis*
  • Stearoyl-CoA Desaturase / isolation & purification
  • Time Factors

Substances

  • Culture Media
  • Recombinant Proteins
  • Iron
  • Stearoyl-CoA Desaturase
  • Glucose
  • Lactose