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Introduction of Bifunctionality into the Multidomain Architecture of the ω-Ester-Containing Peptide Plesiocin.

Authors :
Lee C
Lee H
Park JU
Kim S
Source :
Biochemistry [Biochemistry] 2020 Jan 28; Vol. 59 (3), pp. 285-289. Date of Electronic Publication: 2019 Oct 28.
Publication Year :
2020

Abstract

The modular biosynthetic pathway of ribosomally synthesized and post-translationally modified peptides (RiPPs) enhances their engineering potential for exploring new structures and biological functions. The ω-ester-containing peptides (OEPs), a subfamily of RiPPs, have distinct side-to-side ester or amide linkages and frequently present more than one macrocyclic domain in a "beads-on-a-string" structure. In an effort to improve the engineering potential of RiPPs, we present here the idea that the multidomain architecture of an OEP, plesiocin, can be exploited to create a bifunctional modified peptide. Characterization of plesiocin variants revealed that strong chymotrypsin inhibition relies on the bicyclic structure of the domain in which a leucine residue in the hairpin loop functions as a specificity determinant. Four domains of plesiocin promote simultaneous binding of multiple enzymes, where the C-terminal domain binds chymotrypsin most efficiently. Using this information, we successfully engineered a plesiocin variant in which two different domains inhibit chymotrypsin and trypsin. This result suggests that the multidomain architecture of OEPs is a useful platform for engineering multifunctional hybrid RiPPs.

Details

Language :
English
ISSN :
1520-4995
Volume :
59
Issue :
3
Database :
MEDLINE
Journal :
Biochemistry
Publication Type :
Academic Journal
Accession number :
31644266
Full Text :
https://doi.org/10.1021/acs.biochem.9b00803