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We isolated four congeners of this unprecedented natural product family with the non\u2010cyclized thiamyxin\u2005D fused to a glycerol unit at the C\u2010terminus. 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\u2010(hydroxymethyl)\u20104\u2010methylpent\u20103\u2010enoic acid moiety by a GCN5\u2010related N\u2010acetyltransferase\u2010like 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\u2005nM combined with milder cytotoxic effects on human cell lines indicate the potential for further development of the thiamyxins.<\/jats:p>","DOI":"10.1002\/anie.202212946","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T05:48:57Z","timestamp":1665208137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Thiamyxins: Structure and Biosynthesis of Myxobacterial RNA\u2010Virus Inhibitors**"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-6659","authenticated-orcid":false,"given":"Patrick A.","family":"Haack","sequence":"first","affiliation":[{"name":"Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy Saarland University  Saarbr\u00fccken Germany"},{"name":"German center for infection 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