期刊
ACS SYNTHETIC BIOLOGY
卷 7, 期 3, 页码 896-902出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.7b00396
关键词
synthetic biology; protein production; Pichia pastoris; yeast; antimicrobials
资金
- Ramon Areces Foundation
- FAPESP [2016/24413-0]
- Defense Treat Reduction Agency [DTRA HDTRA1-15-1-0050]
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.
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