The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain

verfasst von: Megha N. Karanth, John P. Kirkpatrick, Joern Krausze, Stefan Schmelz, Andrea Scrima, Teresa Carlomagno
Abstract: In the quest for new bioactive substances, nonribosomal peptide synthetases (NRPS) provide biodiversity by synthesizing nonproteinaceous peptides with high cellular activity. NRPS machinery consists of multiple modules, each catalyzing a unique series of chemical reactions. Incomplete understanding of the biophysical principles orchestrating these reaction arrays limits the exploitation of NRPSs in synthetic biology. Here, we use nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry to solve the conundrum of how intermodular recognition is coupled with loaded carrier protein specificity in the tomaymycin NRPS. We discover an adaptor domain that directly recruits the loaded carrier protein from the initiation module to the elongation module and reveal its mechanism of action. The adaptor domain of the type found here has specificity rules that could potentially be exploited in the design of engineered NRPS machinery.
Organisationseinheit(en): Institut für Organische Chemie
Externe Organisation(en): University of Birmingham
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Typ: Artikel
Journal: Science advances
Band: 10
ISSN: 2375-2548
Publikationsdatum: 21.06.2024
Publikationsstatus: Veröffentlicht
Peer-reviewed: Ja
ASJC Scopus Sachgebiete: Allgemein
Elektronische Version(en): https://doi.org/10.1126/sciadv.adm9404 (Zugang: Offen)

BibTeX

@article{0a67b047ee7b4d709e72100fce8f18db,
title = "The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain",
abstract = "In the quest for new bioactive substances, nonribosomal peptide synthetases (NRPS) provide biodiversity by synthesizing nonproteinaceous peptides with high cellular activity. NRPS machinery consists of multiple modules, each catalyzing a unique series of chemical reactions. Incomplete understanding of the biophysical principles orchestrating these reaction arrays limits the exploitation of NRPSs in synthetic biology. Here, we use nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry to solve the conundrum of how intermodular recognition is coupled with loaded carrier protein specificity in the tomaymycin NRPS. We discover an adaptor domain that directly recruits the loaded carrier protein from the initiation module to the elongation module and reveal its mechanism of action. The adaptor domain of the type found here has specificity rules that could potentially be exploited in the design of engineered NRPS machinery.",
author = "Karanth, {Megha N.} and Kirkpatrick, {John P.} and Joern Krausze and Stefan Schmelz and Andrea Scrima and Teresa Carlomagno",
note = "Publisher Copyright: copyright {\textcopyright} 2024 the Authors, some rights reserved; exclusive.",
year = "2024",
month = jun,
day = "21",
doi = "10.1126/sciadv.adm9404",
language = "English",
volume = "10",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "25",
}