High-level secretion of a wheat lipid transfer protein in Pichia pastoris

Protein Expr Purif. 1998 Jun;13(1):73-82. doi: 10.1006/prep.1998.0888.

Abstract

Plant nonspecific lipid transfer proteins are small basic proteins with eight cysteine residues, all engaged in disulfide bonds. The sequence encoding the wheat 9-kDa LTP was cloned into the secretion vector pYAM7SP8 giving rise to pYTdltp4.90. Production in shake-flasks and a fermentor led to the synthesis of two major species of LTP: a larger than expected species of 14 kDa and a species of 10 kDa, close to the expected size of wheat LTP. When production was carried out in a fermentor with regulation of pH, oxygen level, and feed rate of carbon source, the 10-kDa species was the main protein at the end-point of culture. The recombinant wheat LTP (rLTP), secreted at a level of 720 mg/liter into the culture medium, is soluble. The rLTP was purified to homogeneity by ammonium sulfate precipitation, gel filtration, and anion-exchange chromatography, with a recovery yield of 36%. However, the molecular mass of rLTP, determined by mass spectrometry, is 9996 Da, while its naturally occurring counterpart has a molecular mass of 9607 Da. This discrepancy in size corresponds to a protein carrying three extra amino acids (DKR) at its N-terminal end, and this was confirmed by sequencing. In vitro lipid transfer activity showed that rLTP behaves in a similar way to the naturally occurring protein. These data indicate that Pichia pastoris is an efficient system for production of large quantities of soluble and biologically active rLTP for structure/function analysis.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Plant
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / isolation & purification
  • Chromatography, Gel
  • Chromatography, Ion Exchange
  • Cloning, Molecular
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Pichia / genetics*
  • Plant Proteins
  • Plasmids
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Triticum / metabolism*

Substances

  • Antigens, Plant
  • Carrier Proteins
  • DNA Primers
  • Plant Proteins
  • Recombinant Proteins
  • lipid transfer proteins, plant