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Alternative σ factors in bacteria redirect RNA polymerase to recognize alternative promoters, thereby facilitating coordinated gene expression necessary for adaptive responses. The gene  sig8  ( sav_741 ) in  Streptomyces avermitilis  encodes an alternative σ factor, σ 8 , highly homologous to σ B  in  Streptomyces coelicolor . Studies reported here demonstrate that σ 8  is an important regulator of both avermectin production and stress responses in  S. avermitilis . σ 8  inhibited avermectin production by indirectly repressing expression of cluster-situated activator gene  aveR , and by directly initiating transcription of its downstream gene  sav_742 , which encodes a direct repressor of  ave  structural genes. σ 8  had no effect on cell growth or morphological differentiation under normal growth conditions. Growth of a  sig8- deletion mutant was less than that of wild-type strain on YMS plates following treatment with heat, H 2 O 2 , diamide, NaCl, or KCl.  sig8  transcription was strongly induced by these environmental stresses, indicating response by σ 8  itself. A series of σ 8 -dependent genes responsive to heat, oxidative and osmotic stress were identified by EMSAs, qRT-PCR and  in vitro  transcription experiments. These findings indicate that σ 8  plays an important role in mediating protective responses to various stress conditions by activating transcription of its target genes. Six σ 8 -binding promoter sequences were determined and consensus binding sequence BGVNVH-N 15 -GSNNHH (B: C, T or G, V: A, C or G, S: C or G, H: A, C or T, N: any nucleotide) was identified, leading to prediction of the σ 8  regulon. The list consists of 940 putative σ 8  target genes, assignable to 17 functional groups, suggesting the wide range of cellular functions controlled by σ 8  in  S. avermitilis .

An Alternative σ Factor, σ8, Controls Avermectin Production and Multiple Stress Responses in Streptomyces avermitilis