Characterization of AvaR1, an autoregulator receptor that negatively controls avermectins production in a high avermectin-producing strain

Many γ-butyrolactone-autoregulator receptors control the production of secondary metabolites in Streptomyces spp. Hence, AvaR1, an autoregulator receptor protein in Streptomyces avermitilis, was characterized as a negative regulator of avermectin (Ave) production. Deletion of AvaR1 in a high-producing strain increased production of Ave B1a approx. 1.75 times (~700 μg/ml) compared with the parent strain. Semi-quantitative RT-PCR and electrophoretic mobility shift assays revealed that AvaR1 regulates the biosynthesis of Ave but not through the aveR pathway-specific regulatory gene. A special signaling molecule, avenolide, increased production of Ave. This study has refined our understanding of how avenolide regulates the production of Aves which is promising for developing new methods to improve the production of antibiotics in industrial strains.