Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production

Author(s)

Cao, Jicong ^{[1, 2, 3, 4]} ; de la Fuente-Nunez, Cesar ^{[1, 2, 3, 4]} ; Ou, Rui Wen ^[5] ; Torres, Marcelo Der Torossian ^{[6, 1, 2, 3]} ; Pande, Santosh G. ^[7] ; Sinskey, Anthony J. ^[5] ; Lu, Timothy K. ^{[1, 2, 3, 4]}

Affiliation

^[1] MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[2] MIT, Dept Biol Engn, MIT Synthet Biol Ctr, Synthet Biol Grp, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[3] MIT, Elect Res Lab, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[4] Broad Inst MIT & Harvard, Cambridge, MA 02139 - USA

^[5] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[6] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[7] MIT, Dept Chem Engn, Cambridge, MA 02139 - USA

• Document type: Journal article
• Source: ACS SYNTHETIC BIOLOGY; v. 7, n. 3, p. 896-902, MAR 2018.
• Web of Science Citations: 14

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. (AU)

• FAPESP's process: 16/24413-0 - Antimicrobial and antibiofilm cationic amphipathic peptides
• Grantee: Marcelo Der Torossian Torres
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate