Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production.

TitleYeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production.
Publication TypeJournal Article
Year of Publication2018
AuthorsCao, J, de la Fuente-Nunez, C, Ou, RWen, Torres, MDer Toross, Pande, SG, Sinskey, AJ, Lu, TK
JournalACS Synth Biol
Volume7
Issue3
Pagination896-902
Date Published2018 03 16
ISSN2161-5063
KeywordsAntimicrobial Cationic Peptides, Bioreactors, Fermentation, Humans, Microbial Sensitivity Tests, Pichia, Recombinant Fusion Proteins, Serum Albumin, Synthetic Biology
Abstract

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.

DOI10.1021/acssynbio.7b00396
Alternate JournalACS Synth Biol
Citation Key56
PubMed ID29366323
Grant ListP50 GM098792 / GM / NIGMS NIH HHS / United States