Thiamyxins: Structure and Biosynthesis of Myxobacterial RNA‐Virus Inhibitors**

作者：Patrick A. Haack, Kirsten Harmrolfs, Chantal D. Bader, Ronald Garcia, Antonia P. Gunesch, Sibylle Haid, Alexander Popoff, Alexander Voltz, Heeyoung Kim, Ralf Bartenschlager, Thomas Pietschmann, Rolf Müller · 发表于：Angewandte Chemie International Edition · 年份：2022 · DOI：10.1002/anie.202212946 · 被引用次数：21 · 研究领域：Bacteriophages and microbial interactions、Mycobacterium research and diagnosis、Microbial Natural Products and Biosynthesis

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.