English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Sequential in vitro cyclization by cytochrome P450 enzymes of glycopeptide antibiotic precursors bearing the X-domain from nonribosomal peptide biosynthesis

MPS-Authors
/persons/resource/persons117956

Brieke,  Clara
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons117962

Peschke,  Madeleine
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons117984

Haslinger,  Kristina
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons92561

Cryle,  Max J.
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Brieke, C., Peschke, M., Haslinger, K., & Cryle, M. J. (2015). Sequential in vitro cyclization by cytochrome P450 enzymes of glycopeptide antibiotic precursors bearing the X-domain from nonribosomal peptide biosynthesis. Angewandte Chemie International Edition in English, 54(52), 15715-15719. doi:10.1002/anie.201507533.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002A-21A0-D
Abstract
The biosynthesis of the glycopeptide antibiotics, which include vancomycin and teicoplanin, relies on the interplay between the peptide-producing non-ribosomal peptide synthetase (NRPS) and Cytochrome P450 enzymes (P450s) that catalyze side-chain crosslinking of the peptide. We demonstrate that sequential in vitro P450-catalyzed cyclization of peptide substrates is enabled by the use of an NRPS peptide carrier protein (PCP)-X di-domain as a P450 recruitment platform. This study reveals that whilst the precursor peptide sequence influences the installation of the second crosslink by the P450 OxyAtei , activity is not restricted to the native teicoplanin peptide. Initial peptide cyclization is possible with teicoplanin and vancomycin OxyB homologues, and the latter displays excellent activity with all substrate combinations tested. By using non-natural X-domain substrates, bicyclization of hexapeptides was also shown, which demonstrates the utility of this method for the cyclization of varied peptide substrates in vitro.