Resistance to Enediyne Antitumor Antibiotics by Sequestration (Cell Chemical Biology)

TnmS1, TnmS2, and TnmS3 confer tiancimycin resistance by sequestration. Their homologs are found in all anthraquinone-fused enediyne producers and are widespread in nature, including in the human microbiome. These findings unveil an unprecedented resistance mechanism for the enediynes and should be considered in future efforts to develop enediyne-based chemotherapies.