Carrier proteins boost expression of PR-39-derived peptide in Pichia pastoris

J Appl Microbiol. 2023 Dec 1;134(12):lxad297. doi: 10.1093/jambio/lxad297.

Abstract

Aims: Multidrug resistance presents difficulties in preventing and treating bacterial infections. Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial growth by affecting the intracellular targets rather than by permeabilizing the membrane. The aim of this study was to develop a yeast-based fusion carrier system using calmodulin (CaM) and xylanase (XynCDBFV) as two carriers to express the model PrAMP PR-39-derived peptide (PR-39-DP) in Pichia pastoris.

Methods and results: Fusion protein secreted into the culture supernatant was purified in a one-step on-column digestion using human rhinovirus 3C protease, obtaining the target peptide PR-39-DP. The growth curves of Escherichia coli were monitored by recording the OD600 values of the bacteria. The antibacterial activity of PR-39-DP was evaluated in killing assays performed on E. coli. The yield of PR-39-DP was 1.0-1.2 mg l-1 in the CaM fusion carrier system, approximately three times that of the XynCDBFV fusion carrier system. The minimal inhibitory concentration of PR-39-DP was ∼10.5 µg ml-1.

Conclusions: CaM and XynCDBFV provide increased stability and promote the expression and secretion of active PR-39-DP.

Keywords: Pichia pastoris; PR-39-derived peptide; calmodulin; carrier-assisted expression system; proline-rich antimicrobial peptides; xylanase.

MeSH terms

  • Antimicrobial Cationic Peptides / pharmacology
  • Carrier Proteins* / metabolism
  • Escherichia coli* / metabolism
  • Humans
  • Pichia / genetics
  • Pichia / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomycetales

Substances

  • PR 39
  • Carrier Proteins
  • Antimicrobial Cationic Peptides
  • Recombinant Proteins

Supplementary concepts

  • Komagataella pastoris