Ecm16 protein confers resistance against the DNA intercalator antibiotic echinomycin

Abstract

Echinomycin is a nonribosomal peptide antibiotic that acts by intercalating double‐stranded DNA. The echinomycin biosynthetic gene cluster of Streptomyces lasaliensis contains a gene of unverified function, ecm16. We show that expression of Ecm16 in the echinomycin‐sensitive E. coli K12 renders cells resistant to echinomycin. Additionally, we have determined the X‐ray crystal structure of Ecm16 at 2.0 Å resolution. Interestingly, the three‐dimensional structure of Ecm16 resembles that of UvrA, the DNA damage sensor protein from the prokaryotic nucleotide excision repair pathway. Ecm16, like UvrA, contains two nucleotide binding domains on a single polypeptide chain, and it can bind double‐stranded DNA. However, our results show that neither UvrA nor Ecm16 can complement each other’s function in vivo. Support or Funding Information The University of Texas System STARs Award