Resistance-Guided Mining of Bacterial Genotoxins Defines a Family of DNA Glycosylases.

ABSTRACT: Unique DNA repair enzymes that provide self-resistance against therapeutically important, genotoxic natural products have been discovered in bacterial biosynthetic gene clusters (BGCs). Among these, the DNA glycosylase AlkZ is essential for azinomycin B production and belongs to the HTH_42 superfamily of uncharacterized proteins. Despite their widespread existence in antibiotic producers and pathogens, the roles of these proteins in production of other natural products are unknown. Here, we determine the evolutionary relationship and genomic distribution of all HTH_42 proteins from Streptomyces and use a resistance-based genome mining approach to identify homologs associated with known and uncharacterized BGCs. We find that AlkZ-like (AZL) proteins constitute one distinct HTH_42 sub

SUBMITTER: Bradley NP 

PROVIDER: S-EPMC9040887 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature