Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | eadm9404 |
| Fachzeitschrift | Science advances |
| Jahrgang | 10 |
| Ausgabenummer | 25 |
| Frühes Online-Datum | 19 Juni 2024 |
| Publikationsstatus | Veröffentlicht - 21 Juni 2024 |
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.
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in: Science advances, Jahrgang 10, Nr. 25, eadm9404, 21.06.2024.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain
AU - Karanth, Megha N.
AU - Kirkpatrick, John P.
AU - Krausze, Joern
AU - Schmelz, Stefan
AU - Scrima, Andrea
AU - Carlomagno, Teresa
N1 - Publisher Copyright: copyright © 2024 the Authors, some rights reserved; exclusive.
PY - 2024/6/21
Y1 - 2024/6/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85196684189&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adm9404
DO - 10.1126/sciadv.adm9404
M3 - Article
C2 - 38896613
AN - SCOPUS:85196684189
VL - 10
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 25
M1 - eadm9404
ER -