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 Streptomycesantibiotic regulatory protein (SARP), while the deletion of this gene impaired actinorhodin production. We found the abegenes to be differentially regulated and controlled at multiple levels. Upstream of abeAwas a promoter that directed the transcription of abeABCDat a low but constitutive level. The expression of abeBCDwas, 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 abeBCDpromoter was α- abeA, whose expression mirrored that of abeBCDbut did not require activation by AbeR. Instead, α- abeAtranscript levels were subject to negative control by the double-strand-specific RNase, RNase III.