Projects per year
Abstract
Kistamicin is a divergent member of the glycopeptide antibiotics, a structurally complex class of important, clinically relevant antibiotics often used as the last resort against resistant bacteria. The extensively crosslinked structure of these antibiotics that is essential for their activity makes their chemical synthesis highly challenging and limits their production to bacterial fermentation. Kistamicin contains three crosslinks, including an unusual 15-membered A-O-B ring, despite the presence of only two Cytochrome P450 Oxy enzymes thought to catalyse formation of such crosslinks within the biosynthetic gene cluster. In this study, we characterise the kistamicin cyclisation pathway, showing that the two Oxy enzymes are responsible for these crosslinks within kistamicin and that they function through interactions with the X-domain, unique to glycopeptide antibiotic biosynthesis. We also show that the kistamicin OxyC enzyme is a promiscuous biocatalyst, able to install multiple crosslinks into peptides containing phenolic amino acids.
Original language | English |
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Article number | 2613 |
Number of pages | 15 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 13 Jun 2019 |
Keywords
- biosynthesis
- enzyme mechanisms
- x-ray crystallography
Projects
- 2 Finished
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Improving on nature: diversifying glycopeptide antibiotics to kill the bacterial pathogen Staphylococcus aureus
Cryle, M. (Primary Chief Investigator (PCI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/18 → 31/12/21
Project: Research
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Development of a bio-enabled synthesis for the Glycopeptide Antibiotics
Cryle, M. (Primary Chief Investigator (PCI)) & De Voss, J. J. (Partner Investigator (PI))
Australian Research Council (ARC), Monash University, University of Queensland
1/01/17 → 31/12/19
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 Platform (MPMP)
Schittenhelm, R. (Other) & Steer, D. (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility