The University of Southampton
University of Southampton Institutional Repository

A lanthipeptide library used to identify a protein-protein interaction inhibitor

A lanthipeptide library used to identify a protein-protein interaction inhibitor
A lanthipeptide library used to identify a protein-protein interaction inhibitor
We describe the production and screening of a genetically encoded library of 106 lanthipeptides in Escherichia coli using the substrate tolerant lanthipeptide synthetase ProcM. This plasmid-encoded library was combined with a bacterial reverse two-hybrid system for the interaction of the HIV p6 protein with the UEV domain of the human TSG101 protein, a critical protein-protein interaction for HIV budding from infected cells. Using this approach, we identified an inhibitor of this interaction from the lanthipeptide library, whose activity was verified in vitro and in cell-based virus-like particle budding assays. Given the variety of lanthipeptide backbone scaffolds that may be produced with ProcM, this method may be used for the generation of genetically encoded libraries of natural product-like lanthipeptides containing significant structural diversity. Such libraries may be combined with any cell-based assay for the identification of lanthipeptides with new biological activities.
1552-4450
375-380
Yang, Xiao
6b331ee4-5cc1-487a-9c54-b1527bf7dc21
Lennard, Katherine
1ddd5215-8af1-4654-ac6e-f6ff308403da
He, Chang
7e93a776-9972-4ba7-ab89-e9a4ac5392f4
Walker, Mark
440e66f0-fce4-45cf-a73d-3716f254d87f
Ball, Andrew T.
04031b6f-7446-430b-9494-7561a82600e0
Doigneaux, Cyrielle
9f8adf0b-137e-4642-8cfc-e7e0e556d4b0
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2
van der Donk, Wilfred A.
2aa78f59-8e17-4864-a95d-67a3b7384e48
Yang, Xiao
6b331ee4-5cc1-487a-9c54-b1527bf7dc21
Lennard, Katherine
1ddd5215-8af1-4654-ac6e-f6ff308403da
He, Chang
7e93a776-9972-4ba7-ab89-e9a4ac5392f4
Walker, Mark
440e66f0-fce4-45cf-a73d-3716f254d87f
Ball, Andrew T.
04031b6f-7446-430b-9494-7561a82600e0
Doigneaux, Cyrielle
9f8adf0b-137e-4642-8cfc-e7e0e556d4b0
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2
van der Donk, Wilfred A.
2aa78f59-8e17-4864-a95d-67a3b7384e48

Yang, Xiao, Lennard, Katherine, He, Chang, Walker, Mark, Ball, Andrew T., Doigneaux, Cyrielle, Tavassoli, Ali and van der Donk, Wilfred A. (2018) A lanthipeptide library used to identify a protein-protein interaction inhibitor. Nature Chemical Biology, 14 (4), 375-380. (doi:10.1038/s41589-018-0008-5).

Record type: Article

Abstract

We describe the production and screening of a genetically encoded library of 106 lanthipeptides in Escherichia coli using the substrate tolerant lanthipeptide synthetase ProcM. This plasmid-encoded library was combined with a bacterial reverse two-hybrid system for the interaction of the HIV p6 protein with the UEV domain of the human TSG101 protein, a critical protein-protein interaction for HIV budding from infected cells. Using this approach, we identified an inhibitor of this interaction from the lanthipeptide library, whose activity was verified in vitro and in cell-based virus-like particle budding assays. Given the variety of lanthipeptide backbone scaffolds that may be produced with ProcM, this method may be used for the generation of genetically encoded libraries of natural product-like lanthipeptides containing significant structural diversity. Such libraries may be combined with any cell-based assay for the identification of lanthipeptides with new biological activities.

Text
Yang et al final - Accepted Manuscript
Download (4kB)

More information

Accepted/In Press date: 14 December 2017
e-pub ahead of print date: 5 March 2018
Published date: 28 March 2018

Identifiers

Local EPrints ID: 418730
URI: http://eprints.soton.ac.uk/id/eprint/418730
ISSN: 1552-4450
PURE UUID: cb2007a7-dbe5-49d3-a8c7-bab83ca5204d
ORCID for Ali Tavassoli: ORCID iD orcid.org/0000-0002-7420-5063

Catalogue record

Date deposited: 20 Mar 2018 17:30
Last modified: 15 Sep 2021 01:51

Export record

Altmetrics

Contributors

Author: Xiao Yang
Author: Katherine Lennard
Author: Chang He
Author: Mark Walker
Author: Andrew T. Ball
Author: Cyrielle Doigneaux
Author: Ali Tavassoli ORCID iD
Author: Wilfred A. van der Donk

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×