Regulation of a novel gene cluster involved in secondary metabolite production in Streptomyces coelicolor.
Antibiotic biosynthesis in the streptomycetes is a complex and highly regulated process. Here, we provide evidence for the contribution of a novel genetic locus to antibiotic production in Streptomyces coelicolor. The overexpression of a gene cluster comprising four protein-encoding genes (abeABCD) and an antisense RNA-encoding gene (α-abeA) stimulated the production of the blue-pigmented metabolite actinorhodin on solid medium. Actinorhodin production also was enhanced by the overexpression of an adjacent gene (abeR) encoding a predicted Streptomyces antibiotic regulatory protein (SARP), while the deletion of this gene impaired actinorhodin production. We found the abe genes to be differentially regulated and controlled at multiple levels. Upstream of abeA was a promoter that directed the transcription of abeABCD at a low but constitutive level. The expression of abeBCD was, however, significantly upregulated at a time that coincided with the initiation of aerial development and the onset of secondary metabolism; this expression was activated by the binding of AbeR to four heptameric repeats upstream of a promoter within abeA. Expressed divergently to the abeBCD promoter was α-abeA, whose expression mirrored that of abeBCD but did not require activation by AbeR. Instead, α-abeA transcript levels were subject to negative control by the double-strand-specific RNase, RNase III.
Hindra
Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada.
Pak
Patricia
P
Elliot
Marie A
MA
D000880:Anthraquinones / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D005810:Multigene Family / Q000235:genetics / Q000502:physiology*; D009876:Operon / Q000235:genetics / Q000502:physiology; D055550:Protein Stability; D043244:Ribonuclease III / Q000235:genetics / Q000502:physiology; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism*; D000095622:Benzoisochromanequinones
D000880:Anthraquinones; D001426:Bacterial Proteins; D043244:Ribonuclease III; C013390:actinorhodin; D000095622:Benzoisochromanequinones