A-factor switches on the transcription of adpA, which encodes the

transcriptional activator AdpA, by binding to ArpA, the A-factor receptor protein that binds the adpA promoter, and by releasing DNA-bound ArpA Antidiabetic Compound Library chemical structure (Ohnishi et al., 1999). AdpA activates a number of genes required for morphological development and secondary metabolite formation (the so-called AdpA regulon) (Ohnishi et al., 2005). Key differences exist in the signaling events that initiate morphogenesis in S. coelicolor A3(2) and S. griseus (Chater & Horinouchi, 2003). For example, ramS, which encodes the SapB (lantibiotic-like peptide surfactin) precursor (Kodani et al., 2004), is induced by the bld signaling cascade in S. coelicolor A3(2) (Nguyen et al., 2002), while amfS, which corresponds to ramS (Ueda et al., 2002), is regulated by AdpA (i.e. A-factor) via amfR in S. griseus (Yamazaki check details et al., 2003). In spite of these differences, probable orthologs of all S. coelicolor A3(2) bld genes except the bldK cluster have been identified in the S. griseus genome (Table 1). Because S. griseus contains at least six putative oligopeptide transporters, we previously assumed that the apparent lack of a BldK transporter might be compensated (Ohnishi et al., 2008). Recently, we compared the extracellular proteomes of the WT and ΔadpA strains of S. griseus to identify AdpA-dependent (i.e. A-factor-inducible)

secreted proteins (Akanuma et al., 2009). These included SGR2418, a putative oligopeptide ABC transporter

solute-binding protein in S. griseus. SGR2418 and other components of the ABC transporter are encoded by a putative operon (Fig. 1a). We noticed that this operon was located on the S. griseus chromosome at a position corresponding to the bldK locus in S. coelicolor A3(2), although the order of genes in this operon was different from that in the S. coelicolor A3(2) else bldK operon (Fig. 1a). This observation, combined with its apparent A-factor dependence, prompted us to analyze the function of SGR2418. Because an SGR2418-deficient mutant exhibited a bald phenotype (as described below), we denoted the SGR2414, SGR2415, SGR2416, SGR2417, and SGR2418 genes as bldKE, bldKD, bldKA, bldKC, and bldKB, respectively, after the bldK genes in S. coelicolor A3(2). In S. coelicolor A3(2), bldKA and bldKC encode permeases, and bldKD and bldKE ATPases. Together with the solute-binding protein BldKB, they comprise the BldK ABC transporter (Nodwell et al., 1996). Hereafter, to discriminate between corresponding genes (and their products) in S. griseus and S. coelicolor A3(2), we have suffixed their names with -g or -c. Streptomyces griseus IFO13350 (=NBRC102592) was obtained from the Institute of Fermentation [(IFO), Osaka, Japan]. The S. griseusΔadpA and ΔafsA mutants have been described previously (Ohnishi et al., 1999; Kato et al., 2007).