biostudies-literatureHaack PADeutsche Forschungsgemeinschafte202212946https://www.ebi.ac.uk/biostudies/studies/S-EPMC10100342biostudies-literatureUnknown61(52)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 infecAngewandte Chemie (International ed. in English)Thiamyxins: Structure and Biosynthesis of Myxobacterial RNA-Virus Inhibitors.PMC10100342EXC 2155 - project number 390874280Voltz AHarmrolfs KHaid SPopoff AKim HGunesch APMuller RGarcia RHaack PABader CDPietschmann TBartenschlager RfalseThiamyxins: Structure and Biosynthesis of Myxobacterial RNA-Virus Inhibitors.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 infec2022-01-01T00:00:00Z2022 Dec2026-06-05T06:48:33.495Z2025-02-18T23:40:43.347ZS-EPMC101003423620811710.1002/anie.202212946