griseus is unknown. The expression of all of bldN, SLI6392, SLI1868 and the SCO2921 ortholog (gene detected in S. lividans genome but not named in StrepDB

Buparlisib order [7]) is influenced by adpA deletion in S. lividans. It remains to be determined whether AdpA directly controls S. lividans adpA and bldA as described in S. coelicolor and griseus[16, 23]. S. coelicolor adpA is one of 145 identified TTA-containing genes; the production of the proteins encoded by these genes is dependent on bldA, encoding the only tRNA for the rare leucine codon TTA [46]. Our study has revealed that expression of 11 TTA-containing genes and of 24 genes regulated by S. coelicolor bldA[42, 47, 48] was affected by adpA deletion in S. lividans (Additional files 4: Table FDA approved Drug Library supplier S3). We show that cchA, cchB, sti1, hyaS, SLI6586 and SLI6587, previously identified in S. coelicolor as bldA-dependent genes, are direct targets of S. lividans AdpA [25]. Of the 29 other bldA-dependent genes, 19 are probable direct S. lividans AdpA targets: in silico analysis indicated the presence

of putative AdpA-binding sites upstream from these genes (most of them with score above 4, see Additional file 5: Table S4). By analogy, this suggests that the deregulation of certain genes observed in the S. coelicolor bldA mutant may have been the consequence of S. coelicolor AdpA down-regulation, as previously suggested [49]. To predict probable direct targets of AdpA in S. lividans and contribute to knowledge of the AdpA regulon, we carried out in silico analysis of the entire S. coelicolor genome using PREDetector [39], and also restricted to the S. lividans genes identified as being AdpA-dependent (see Additional file 5: Table S4 and Table 3). We identified 95 genes probably directly activated by S. lividans AdpA and 67 genes that could be directly repressed (Additional file 5: Table S4). Most of the putative AdpA-binding sites identified by this analysis

are coherent with the findings of Yao et al., demonstrating the importance of G and C nucleotides at positions 2 and 4, respectively [50]. Six genes have been identified as directly regulated by AdpA in other species (adpA, bldN, wblA, SLI6392, SCO2921 orthologs, and glpQ1, as indicated in Table 3 in bold) [10, very 12, 15, 16, 18], and 27 more in S. griseus are also probable AdpA-direct targets (e.g. cchB, SLI0755-0754 operon, rarA operon, scoF4, groEL1, SLI6587, SLI4345, cydAB, and ectABD, as indicated in Table 3 and Additional file 2: Table S2, underlined) [7, 12–14]. Sixty-three of the 162 probable direct targets of AdpA in S. lividans have no ortholog in the S. griseus genome (Additional file 5: Table S4). Table 3 Genes putatively directly regulated by S. lividans AdpA in liquid rich medium a Geneb Geneb Geneb Gene nameb cis-elementc Scorec Positionc Fcd Classe Probably directly activated by S.