A sulfur-containing nucleoside antibiotic from <i>Photorhabdus</i>.

ABSTRACT: We report the discovery of 4'-thiothymidine (4'sT), a sulfur-containing nucleoside antibiotic produced by the nematode symbiont Photorhabdus asymbiotica. 4'sT exhibits antibacterial activity against Escherichia coli, Stenotrophomonas maltophilia, and Klebsiella pneumoniae. The production of 4'sT was increased in rifampicin-resistant mutants. Heterologous expression of the radical SAM enzyme-containing gene cluster confirmed its biosynthetic origin. Resistant mutants mapped to tdk, which encodes thymidine kinase in the thymidine salvage pathway. Mechanistic studies revealed that 4'sT is a prodrug activated via the thymidine salvage pathway and incorporated into DNA, where it inhibits replication and triggers the SOS response. Clinical E. coli isolat

SUBMITTER: Son S 

PROVIDER: S-EPMC12691670 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature