Structural highlights
Publication Abstract from PubMed
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.
The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain.,Karanth MN, Kirkpatrick JP, Krausze J, Schmelz S, Scrima A, Carlomagno T Sci Adv. 2024 Jun 21;10(25):eadm9404. doi: 10.1126/sciadv.adm9404. Epub 2024 Jun , 19. PMID:38896613[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Karanth MN, Kirkpatrick JP, Krausze J, Schmelz S, Scrima A, Carlomagno T. The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain. Sci Adv. 2024 Jun 21;10(25):eadm9404. PMID:38896613 doi:10.1126/sciadv.adm9404
