Title | Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Cao, J, de la Fuente-Nunez, C, Ou, RWen, Torres, MDer Toross, Pande, SG, Sinskey, AJ, Lu, TK |
Journal | ACS Synth Biol |
Volume | 7 |
Issue | 3 |
Pagination | 896-902 |
Date Published | 2018 Mar 16 |
ISSN | 2161-5063 |
Keywords | Antimicrobial 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. |
DOI | 10.1021/acssynbio.7b00396 |
Alternate Journal | ACS Synth Biol |
Citation Key | 56 |
PubMed ID | 29366323 |
Grant List | P50 GM098792 / GM / NIGMS NIH HHS / United States |