Projects per year
Abstract
The activity of glycopeptide antibiotics (GPAs) depends upon important structural modifications to their precursor heptapeptide backbone: specifically, the cytochrome P450-catalyzed oxidative cross-linking of aromatic side chains as well as the halogenation of specific residues within the peptide. The timing of halogenation and its effect on the cyclization of the peptide are currently unclear. Our results show that chlorination of peptide precursors improves their processing by P450 enzymes in vitro, which provides support for GPA halogenation occurring prior to peptide cyclization during nonribosomal peptide synthesis. We could also determine that the activity of the second enzyme in the oxidative cyclization cascade, OxyA, remains higher for chlorinated peptide substrates even when the biosynthetic GPA product possesses an altered chlorination pattern, which supports the role of the chlorine atoms in orienting the peptide substrate in the active site of these enzymes.
Original language | English |
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Pages (from-to) | 1239-1247 |
Number of pages | 9 |
Journal | Biochemistry |
Volume | 56 |
Issue number | 9 |
DOIs | |
Publication status | Published - 7 Mar 2017 |
Projects
- 2 Finished
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Development of a bio-enabled synthesis for the Glycopeptide Antibiotics
Cryle, M. & De Voss, J.
Australian Research Council (ARC), Monash University, University of Queensland
1/01/17 → 31/12/19
Project: Research
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ARC Centre of Excellence in Advanced Molecular Imaging
Whisstock, J., Abbey, B., Nugent, K., Quiney, H. M., Godfrey, D. I., Heath, W., Fairlie, D., Chapman, H., Peele, A., Davey, J. & Wittmann, A.
30/06/14 → 31/03/21
Project: Research
Equipment
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Australian Synchrotron
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility
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Monash Proteomics & Metabolomics Facility
Ralf Schittenhelm (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility