Kistamicin biosynthesis reveals the biosynthetic requirements for production of highly crosslinked glycopeptide antibiotics.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 06 2019
13 06 2019
Historique:
received:
10
10
2018
accepted:
07
05
2019
entrez:
15
6
2019
pubmed:
15
6
2019
medline:
10
7
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31197182
doi: 10.1038/s41467-019-10384-w
pii: 10.1038/s41467-019-10384-w
pmc: PMC6565677
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Glycopeptides
0
Peptides
0
kistamicin A
155683-50-4
Cytochrome P-450 Enzyme System
9035-51-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2613Subventions
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : FT120100632
Pays : International
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : DP180103047
Pays : International
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : DP170102220
Pays : International
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TP-A03
Pays : International
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : APP1140619
Pays : International
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