{"doi":"10.1021/jacs.2c08816","title":"The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition","abstract":"High Resolution Image Download MS PowerPoint Slide Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against Mycobacterium tuberculosis . To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent.","journal":"Journal of the American Chemical Society","year":2023,"id":360004,"datarank":0.4051937681692582,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.05980600422015127,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.05980600422015127,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":7,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1005477,"name":"Ullrich Scheid","orcid":null,"position":1,"is_corresponding":false},{"id":1005478,"name":"Teresa Kösel","orcid":null,"position":2,"is_corresponding":false},{"id":461534,"name":"Jennifer Herrmann","orcid":"0000-0003-3398-9938","position":3,"is_corresponding":false},{"id":1005176,"name":"Daniel Krug","orcid":"0000-0002-3664-1884","position":4,"is_corresponding":false},{"id":245781,"name":"Helena I. 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