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

Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production.

Author information

1
Synthetic Biology Group, MIT Synthetic Biology Center, Department of Biological Engineering, and Department of Electrical Engineering and Computer Science , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
2
Research Laboratory of Electronics , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
3
The Broad Institute of MIT and Harvard , Cambridge , Massachusetts 02139 , United States.
4
Department of Biology , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
5
Centro de Ciências Naturais e Humanas , Universidade Federal do ABC , Santo André , SP 09210580 , Brazil.
6
Department of Chemical Engineering , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.

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.

KEYWORDS:

Pichia pastoris; antimicrobials; protein production; synthetic biology; yeast

PMID:
29366323
DOI:
10.1021/acssynbio.7b00396
[Indexed for MEDLINE]

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