Enhancement of lipase r27RCL production in Pichia pastoris by regulating gene dosage and co-expression with chaperone protein disulfide isomerase

Enzyme Microb Technol. 2013 Dec 10;53(6-7):438-43. doi: 10.1016/j.enzmictec.2013.09.009. Epub 2013 Sep 30.

Abstract

Pichia pastoris has been successfully used in the production of many secreted and intracellular recombinant proteins, but there is still a large room of improvement for this expression system. Two factors drastically influence the lipase r27RCL production from Rhizopus chinensis CCTCC M201021, which are gene dosage and protein folding in the endoplasmic reticulum (ER). Regarding the effect of gene dosage, the enzyme activity for recombinant strain with three copies lipase gene was 1.95-fold higher than that for recombinant strain with only one copy lipase gene. In addition, the lipase production was further improved by co-expression with chaperone PDI involved in the disulfide bond formation in the ER. Overall, the maximum enzyme activity reached 355U/mL by the recombinant strain with one copy chaperone gene PDI plus five copies lipase gene proRCL in shaking flasks, which was 2.74-fold higher than that for the control strain with only one copy lipase gene. Overall, co-expression with PDI vastly increased the capacity for processing proteins of ER in P. pastoris.

Keywords: Chaperone PDI; Gene dosage; Lipase; Pichia pastoris.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / metabolism
  • Fungal Proteins / biosynthesis*
  • Fungal Proteins / genetics*
  • Gene Dosage
  • Gene Expression
  • Genes, Fungal
  • Genetic Engineering
  • Lipase / biosynthesis*
  • Lipase / genetics*
  • Molecular Chaperones / biosynthesis
  • Molecular Chaperones / genetics
  • Pichia / enzymology*
  • Pichia / genetics*
  • Protein Disulfide-Isomerases / biosynthesis*
  • Protein Disulfide-Isomerases / genetics*
  • Protein Folding
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Rhizopus / enzymology
  • Rhizopus / genetics

Substances

  • Fungal Proteins
  • Molecular Chaperones
  • Recombinant Proteins
  • Lipase
  • Protein Disulfide-Isomerases