Bacterial Display and Screening of Posttranslationally Thioether-Stabilized Peptides

被引：34

作者：

Bosma, Tjibbe ^{[1
]}

Kuipers, Anneke ^{[1
]}

Bulten, Erna ^{[1
]}

de Vries, Louwe ^{[1
]}

Rink, Rick ^{[1
]}

Moll, Gert N. ^{[1
]}

机构：

[1] LanthioPep, NL-9747 AG Groningen, Netherlands

来源：

APPLIED AND ENVIRONMENTAL MICROBIOLOGY | 2011年 / 77卷 / 19期

关键词：

DEHYDRO-AMINO-ACIDS; SURFACE DISPLAY; PHAGE DISPLAY; LACTOCOCCUS; PROTEIN; BIOSYNTHESIS; LIBRARIES; NISIN; EXPRESSION; TRANSPORT;

D O I：

10.1128/AEM.05550-11

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

A major hurdle in the application of therapeutic peptides is their rapid degradation by peptidases. Thioether bridges effectively protect therapeutic peptides against breakdown, thereby strongly increasing bioavailability, enabling oral and pulmonary delivery and potentially significantly optimizing the receptor interaction of selected variants. To efficiently select optimal variants, a library of DNA-coupled thioether-bridged peptides is highly desirable. Here, we present a unique cell surface display system of thioether-bridged peptides and successfully demonstrate highly selective screening. Peptides are posttranslationally modified by thioether bridge-installing enzymes in Lactococcus lactis, followed by export and sortase-mediated covalent coupling to the lactococcal cell wall. This allows the combinatorial optimization and selection of medically and economically highly important therapeutic peptides with strongly enhanced therapeutic potential.

引用

页码：6794 / 6801

页数：8