Overexpression of SAV111 in Streptomyces avermitilis increases avermectin production by binding to aveA1 gene promoter

Abstract

Abstract Background Avermectin antibiotics from Streptomyces avermitilis are used widely in medicine and agriculture. The LuxR family transcription regulators modulate antibiotic biosynthesis in addition to regulating virulence factor expression, biofilm formation, and the hosts′ immune response. At present, there was no report about the regulation of LuxR family proteins on avermection production. Results We investigated the mechanism by which overexpression of SAV111, a LuxR family regulator, promoted avermectin production. Shaking flask fermentation of the SAV111 overexpression strain verified that SAV111 promotes avermectin biosynthesis, and indicated SAV111 stimulates cell growth. Streaking experiments showed earlier emergence of morphological differentiation of the SAV111 overexpression strain. Electrophoretic mobility shift assays indicated that SAV111 mainly affects avermectin production by binding to the promoter region of aveA1, a type I polyketide synthase gene in the avermectin biosynthesis pathway. Conclusions Results from this work showed that SAV111 promotes avermectin production, cell growth and morphological differentiation in S. avermitilis. Overexpression of SAV111 improves avermectin production mainly by promoting aveA1 transcription. Our findings will expand the regulation network of avermectin biosynthesis and provide a theoretical basis for constructing high-yield strains.