Partial loss of self-resistance to daunorubicin in drrD mutant of Streptomyces peucetius

• Authentic drrD deletion-disruption mutant strain of S. peucetius was constructed.
• DrrD mutation was not lethal to the cell and the biomass production was unaffected.
• Self-resistance assay reveals that drrD mutant is more sensitive to daunorubicin.
• DrrD interacts with FAD effectively.
• DrrD protein may modify the drug to inactive form and thus provide self-resistance.

Self-resistance is a key element for survival of antibiotic producing Streptomyces. Self-resistance in Streptomyces peucetius is conferred by drrA, drrB and drrC genes to survive the toxicity of daunorubicin produced by the organism. The fourth gene is drrD, which is found in drrAB operon and was reported as a possible self-resistance gene. In this study, a drrD mutant is constructed, which showed loss of self-resistance partially to daunorubicin. This study establishes drrD gene as self-resistance gene and along with drrA, drrB and drrC it forms the full complement of self-resistance that protects S. peucetius from the toxicity of daunorubicin. Bioinformatics analysis of DrrD protein showed that it has N-terminal FAD binding domain. It belongs to a family of proteins that does oxidoreductase and transferase activity. DrrD shares high similarity with FAD binding AknOx protein of S. galilaeus, the aclacinomycin producer. DrrD protein was expressed and the partially purified protein was able to bind to FAD. AknOx binds to sugar moiety of aclacinomycin and modifies it to a temporary inactive form and similar role for DrrD is discussed.

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