Specificity and Application of the Lantibiotic Protease NisP

Frontiers in Microbiology
Manuel Montalbán-LópezOscar P Kuipers

Abstract

Lantibiotics are ribosomally produced and posttranslationally modified peptides containing several lanthionine residues. They exhibit substantial antimicrobial activity against Gram-positive bacteria, including relevant pathogens. The production of the model lantibiotic nisin minimally requires the expression of the modification and export machinery. The last step during nisin maturation is the cleavage of the leader peptide. This liberates the active compound and is catalyzed by the cell wall-anchored protease NisP. Here, we report the production and purification of a soluble variant of NisP. This has enabled us to study its specificity and test its suitability for biotechnological applications. The ability of soluble NisP to cleave leaders from various substrates was tested with two sets of nisin variants. The first set was designed to investigate the influence of amino acid variations in the leader peptide or variations around the cleavage site. The second set was designed to study the influence of the lanthionine ring topology on the proteolytic efficiency. We show that the substrate promiscuity is higher than has previously been suggested. Our results demonstrate the importance of the arginine residue at the end of the lea...Continue Reading

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Citations

Jan 17, 2020·Expert Opinion on Drug Discovery·Stephanie Kate Sandiford
Sep 17, 2020·Natural Product Reports·Manuel Montalbán-LópezWilfred A van der Donk
Apr 2, 2020·Journal of Bacteriology·Delphine DufourCéline M Lévesque
Apr 8, 2018·Applied and Environmental Microbiology·Qian LiOscar P Kuipers
Jan 11, 2019·Journal of Industrial Microbiology & Biotechnology·Maximilian J HelfJörn Piel
Oct 17, 2019·Frontiers in Microbiology·Rubén CebriánOscar P Kuipers
Apr 3, 2019·Nature Chemical Biology·Steven SchmittSven Panke
Feb 1, 2019·Scientific Reports·Marcel LagedrosteLutz Schmitt
Dec 1, 2020·Frontiers in Microbiology·Hamid Reza Karbalaei-Heidari, Nediljko Budisa
Mar 4, 2020·Biochimica Et Biophysica Acta. Biomembranes·Xiaoqi WangEefjan Breukink
Jun 3, 2021·International Journal of Molecular Sciences·Patricia Alvarez-SieiroBert Poolman
May 9, 2021·Applied and Environmental Microbiology·Anton Du Preez van StadenCarine Smith
Sep 26, 2019·ACS Synthetic Biology·Anton Du Preez Van StadenCarine Smith
Aug 31, 2021·RSC Chemical Biology·Julian D Hegemann, Roderich D Süssmuth
Nov 19, 2021·Frontiers in Cellular and Infection Microbiology·Murtadha Q AliSven Hammerschmidt

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Methods Mentioned

BETA
PCR
reverse phase chromatography
affinity

Software Mentioned

GeneArt

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