Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production

ACS Synth Biol. 2018 Mar 16;7(3):896-902. doi: 10.1021/acssynbio.7b00396. Epub 2018 Feb 12.


Antibiotic resistance is one of the most challenging global health threats in our society. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics for the treatment of drug-resistant infections. However, they are limited by their high manufacturing cost. Engineering living organisms represents a promising approach to produce such molecules in an inexpensive manner. Here, we genetically modified the yeast Pichia pastoris to produce the prototypical AMP apidaecin Ia using a fusion protein approach that leverages the beneficial properties ( e.g., stability) of human serum albumin. The peptide was successfully isolated from the fusion protein construct, purified, and demonstrated to have bioactivity against Escherichia coli. To demonstrate this approach as a manufacturing solution to AMPs, we scaled-up production in bioreactors to generate high AMP yields. We envision that this system could lead to improved AMP biomanufacturing platforms.

Keywords: Pichia pastoris; antimicrobials; protein production; synthetic biology; yeast.

Publication types

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

MeSH terms

  • Antimicrobial Cationic Peptides / biosynthesis*
  • Antimicrobial Cationic Peptides / isolation & purification
  • Antimicrobial Cationic Peptides / pharmacology
  • Bioreactors / microbiology
  • Fermentation
  • Humans
  • Microbial Sensitivity Tests
  • Pichia / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Serum Albumin / metabolism
  • Synthetic Biology / methods*


  • Antimicrobial Cationic Peptides
  • Recombinant Fusion Proteins
  • Serum Albumin
  • apidaecin