Self‐Resistance to an Antitumor Antibiotic: A DNA Glycosylase Triggers the Base‐Excision Repair System in Yatakemycin Biosynthesis

Abstract

Resistance is (not) futile: The yatakemycin biosynthetic gene cluster involves the ytkR2 gene, which encodes a protein with homology to a recently discovered bacterial DNA glycosylase. Genetic validation in vivo, biochemical assays, and in vitro mutagenesis studies revealed that YtkR2 confers resistance for the bacteria by specifically recognizing and cleaving the YTM-modified base (see scheme).