Thiamyxins: Structure and Biosynthesis of Myxobacterial RNA-Virus Inhibitors.
Antiviral Agents
Biosynthesis
Depsipeptides
Natural Products
Structure Elucidation
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
23 12 2022
23 12 2022
Historique:
received:
01
09
2022
pubmed:
9
10
2022
medline:
17
12
2022
entrez:
8
10
2022
Statut:
ppublish
Résumé
During our search for novel myxobacterial natural products, we discovered the thiamyxins: thiazole- and thiazoline-rich non-ribosomal peptide-polyketide hybrids with potent antiviral activity. We isolated four congeners of this unprecedented natural product family with the non-cyclized thiamyxin D fused to a glycerol unit at the C-terminus. Alongside their structure elucidation, we present a concise biosynthesis model based on biosynthetic gene cluster analysis and isotopically labelled precursor feeding. We report incorporation of a 2-(hydroxymethyl)-4-methylpent-3-enoic acid moiety by a GCN5-related N-acetyltransferase-like decarboxylase domain featuring polyketide synthase. The thiamyxins show potent inhibition of RNA viruses in cell culture models of corona, zika and dengue virus infection. Their potency up to a half maximal inhibitory concentration of 560 nM combined with milder cytotoxic effects on human cell lines indicate the potential for further development of the thiamyxins.
Identifiants
pubmed: 36208117
doi: 10.1002/anie.202212946
pmc: PMC10100342
doi:
Substances chimiques
RNA
63231-63-0
Polyketide Synthases
79956-01-7
Polyketides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202212946Informations de copyright
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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