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Gene Review

bldA  -  tRNA

Streptomyces coelicolor A3(2)

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Disease relevance of bldA

  • One candidate for such a gene was bldH, because the bldH109 mutant of Streptomyces coelicolor resembles bldA mutants in some aspects [1].
  • Sequence analysis of the gene, designated leuU, indicated that it codes for a tRNA 88 nucleotides in length that shares 75% identity with the Escherichia coli tRNA(Leu)CUC, while it shares only 65% identity with the only other sequenced leucyl tRNA from S. coelicolor, the bldA encoded tRNA(Leu)UUA [2].

High impact information on bldA

  • Site-directed mutagenesis of carB, changing its two TTA codons to CTC (leucine) codons, resulted in bldA-independent expression; hence the bldA product is the principal tRNA for the UUA codon [3].
  • In Streptomyces coelicolor A3(2) and the related species Streptomyces lividans 66, aerial mycelium formation and antibiotic production are blocked by mutations in bldA, which specifies a tRNA(Leu)-like gene product which would recognize the UUA codon [3].
  • Two other genes (hyg and aad) containing TTA codons show a medium-dependent reduction in phenotypic expression (hygromycin resistance and spectinomycin resistance, respectively) in bldA mutants [3].
  • RNA analysis and gene fusions showed that one of the TTA-containing genes is part of a large bldA-dependent operon, the gene products of which include three proteins isolated from the spore surface by detergent washing (SapC, D and E), and several probable metabolic enzymes [4].
  • A rare leucine codon in adpA is implicated in the morphological defect of bldA mutants of Streptomyces coelicolor [1].

Chemical compound and disease context of bldA


Biological context of bldA

  • A constructed in frame deletion of adpAc conferred a bald colony phenotype, and the mutant behaved like bldA mutants and bldH109 in its pattern of extracellular signal exchange [1].
  • This dependence was shown to be mediated via the TTA-containing regulatory gene adpA, also known as bldH, a developmental gene that is responsible for the effects of bldA on differentiation [8].
  • Thus, we concluded that the melC operon is under general direct positive control by AdpA family proteins, perhaps at the transcriptional level and certainly at the translational level via bldA, in Streptomyces [9].
  • We identified adpA as an araC-like regulatory gene needed for colonial morphogenesis in Streptomyces coelicolor and showed that its activity depended on a unique TTA triplet corresponding to the leucyl-tRNA gene (bldA) [10].
  • Moreover, translational fusions of the 5' end of actII-ORF4 that included the UUA codon to the ermE reporter gene demonstrated the presence of functional bldA tRNA in young, exponentially growing cultures and no increase in the efficiency of translation of UUA codons, relative to UUG codons, was observed during growth [11].

Associations of bldA with chemical compounds

  • Bald (bld) mutants fail to form aerial mycelium under at least some conditions. bldA encodes the only tRNA species able to read the leucine codon UUA efficiently, implying the involvement of a TTA-containing gene in initiating aerial growth [1].
  • A single TTA codon in redZ provided a potential explanation for the bldA-dependence of undecylprodigiosin synthesis [12].
  • Like the previously defined bldA mutants, the bldG and bldH mutants were developmentally blocked on glucose [13].
  • On the basis of this screening analysis and the subsequent complementation analysis of the mutants obtained we assigned developmental roles to a gene involved in methionine biosynthesis (metH) and two previously uncharacterized genes (SCO6938 and SCO2525) and we reidentified two previously described developmental genes (bldA and bldM) [14].

Other interactions of bldA

  • SCO0762, a serine-protease inhibitor belonging to the Streptomyces subtilisin inhibitor family implicated in differentiation in other streptomycetes, was completely absent from the bldA mutant [8].
  • It also implied that translational arrest at the UUA codon in adpAc mRNA caused a polar effect on the downstream ornA, and that the poor translation of both genes contributes extensively to the deficiency of aerial mycelium formation in bldA mutants [1].
  • Evidence for the control of a cluster of function-unknown genes by the SCO4263 regulator revealed a new aspect of the pleiotropic bldA phenotype [15].
  • Sporulation of a subset of Sg bald mutants, which produce no aerial mycelium or spores, was restored in the presence of bldA from Sc or Sg [16].

Analytical, diagnostic and therapeutic context of bldA

  • Accumulation of the leuU tRNA was examined by Northern blot analysis and shown to be present at constant levels throughout growth in contrast to the bldA-encoded tRNA which shows a temporal pattern of accumulation [Leskiw et al., 1993. J. Bacteriol., 175, 1995-2005] [2].


  1. A rare leucine codon in adpA is implicated in the morphological defect of bldA mutants of Streptomyces coelicolor. Takano, E., Tao, M., Long, F., Bibb, M.J., Wang, L., Li, W., Buttner, M.J., Bibb, M.J., Deng, Z.X., Chater, K.F. Mol. Microbiol. (2003) [Pubmed]
  2. Use of polymerase chain reaction to identify a leucyl tRNA in Streptomyces coelicolor. Trepanier, N.K., Nguyen, G.D., Leedell, P.J., Leskiw, B.K. Gene (1997) [Pubmed]
  3. TTA codons in some genes prevent their expression in a class of developmental, antibiotic-negative, Streptomyces mutants. Leskiw, B.K., Lawlor, E.J., Fernandez-Abalos, J.M., Chater, K.F. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  4. SCP1, a 356,023 bp linear plasmid adapted to the ecology and developmental biology of its host, Streptomyces coelicolor A3(2). Bentley, S.D., Brown, S., Murphy, L.D., Harris, D.E., Quail, M.A., Parkhill, J., Barrell, B.G., McCormick, J.R., Santamaria, R.I., Losick, R., Yamasaki, M., Kinashi, H., Chen, C.W., Chandra, G., Jakimowicz, D., Kieser, H.M., Kieser, T., Chater, K.F. Mol. Microbiol. (2004) [Pubmed]
  5. bldA dependence of undecylprodigiosin production in Streptomyces coelicolor A3(2) involves a pathway-specific regulatory cascade. White, J., Bibb, M. J. Bacteriol. (1997) [Pubmed]
  6. Induction of actinorhodin production by rpsL (encoding ribosomal protein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2). Shima, J., Hesketh, A., Okamoto, S., Kawamoto, S., Ochi, K. J. Bacteriol. (1996) [Pubmed]
  7. The positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus is mistranslated in a bldA mutant. Trepanier, N.K., Jensen, S.E., Alexander, D.C., Leskiw, B.K. Microbiology (Reading, Engl.) (2002) [Pubmed]
  8. Changes in the extracellular proteome caused by the absence of the bldA gene product, a developmentally significant tRNA, reveal a new target for the pleiotropic regulator AdpA in Streptomyces coelicolor. Kim, D.W., Chater, K., Lee, K.J., Hesketh, A. J. Bacteriol. (2005) [Pubmed]
  9. Expression of the melC operon in several Streptomyces strains is positively regulated by AdpA, an AraC family transcriptional regulator involved in morphological development in Streptomyces coelicolor. Zhu, D., He, X., Zhou, X., Deng, Z. J. Bacteriol. (2005) [Pubmed]
  10. Colonial differentiation in Streptomyces coelicolor depends on translation of a specific codon within the adpA gene. Nguyen, K.T., Tenor, J., Stettler, H., Nguyen, L.T., Nguyen, L.D., Thompson, C.J. J. Bacteriol. (2003) [Pubmed]
  11. Stationary-phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated. Gramajo, H.C., Takano, E., Bibb, M.J. Mol. Microbiol. (1993) [Pubmed]
  12. A response-regulator-like activator of antibiotic synthesis from Streptomyces coelicolor A3(2) with an amino-terminal domain that lacks a phosphorylation pocket. Guthrie, E.P., Flaxman, C.S., White, J., Hodgson, D.A., Bibb, M.J., Chater, K.F. Microbiology (Reading, Engl.) (1998) [Pubmed]
  13. New loci required for Streptomyces coelicolor morphological and physiological differentiation. Champness, W.C. J. Bacteriol. (1988) [Pubmed]
  14. Novel genes that influence development in Streptomyces coelicolor. Gehring, A.M., Wang, S.T., Kearns, D.B., Storer, N.Y., Losick, R. J. Bacteriol. (2004) [Pubmed]
  15. Effects of growth phase and the developmentally significant bldA-specified tRNA on the membrane-associated proteome of Streptomyces coelicolor. Kim, D.W., Chater, K.F., Lee, K.J., Hesketh, A. Microbiology (Reading, Engl.) (2005) [Pubmed]
  16. Identification of bldA mutants of Streptomyces griseus. Kwak, J., McCue, L.A., Kendrick, K.E. Gene (1996) [Pubmed]
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