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

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Megha N. Karanth
  • John P. Kirkpatrick
  • Joern Krausze
  • Stefan Schmelz
  • Andrea Scrima
  • Teresa Carlomagno

Research Organisations

External Research Organisations

  • University of Birmingham
  • Helmholtz Centre for Infection Research (HZI)
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Details

Original languageEnglish
Article numbereadm9404
JournalScience advances
Volume10
Issue number25
Early online date19 Jun 2024
Publication statusPublished - 21 Jun 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.

ASJC Scopus subject areas

Cite this

The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain. / Karanth, Megha N.; Kirkpatrick, John P.; Krausze, Joern et al.
In: Science advances, Vol. 10, No. 25, eadm9404, 21.06.2024.

Research output: Contribution to journalArticleResearchpeer review

Karanth, MN, Kirkpatrick, JP, Krausze, J, Schmelz, S, Scrima, A & Carlomagno, T 2024, 'The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain', Science advances, vol. 10, no. 25, eadm9404. https://doi.org/10.1126/sciadv.adm9404
Karanth, M. N., Kirkpatrick, J. P., Krausze, J., Schmelz, S., Scrima, A., & Carlomagno, T. (2024). The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain. Science advances, 10(25), Article eadm9404. https://doi.org/10.1126/sciadv.adm9404
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. Science advances. 2024 Jun 21;10(25):eadm9404. Epub 2024 Jun 19. doi: 10.1126/sciadv.adm9404
Karanth, Megha N. ; Kirkpatrick, John P. ; Krausze, Joern et al. / The specificity of intermodular recognition in a prototypical nonribosomal peptide synthetase depends on an adaptor domain. In: Science advances. 2024 ; Vol. 10, No. 25.
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