TTA Codons in Some Genes Prevent Their Expression in a Class of Developmental, Antibiotic-Negative, Streptomyces Mutants

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 6; pp. 2461 - 2465
• Main Authors: Leskiw, B. K., Lawlor, E. J., Fernandez-Abalos, J. M., Chater, K. F.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.03.1991; National Acad Sciences
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteriology; Bacteriophages; Base Sequence; beta-Galactosidase - genetics; beta-Lactamases - genetics; Biological and medical sciences; Carbohydrates; Cinnamates; Codon - genetics; Codons; DNA; Drug Resistance, Microbial - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; Genes; Genes, Bacterial; Genetic mutation; Genetics; Hygromycin B - analogs & derivatives; Hygromycin B - pharmacology; Leucine; Microbiology; Molecular Sequence Data; Plasmids; Restriction Mapping; RNA, Transfer - genetics; Spectinomycin - pharmacology; Streptomyces; Streptomyces - drug effects; Streptomyces - enzymology; Streptomyces - genetics; Streptomyces coelicolor; Streptomyces lividans; Transfer RNA; Streptomycetaceae; Streptomyces coelicolor; Use; Gene expression; Actinomycetales; Resistance; Antibiotic; Regulation(control); Codon; t-RNA; Development; Streptomyces lividans; Bacteria; Actinomycetes; Mutation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.6.2461

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 tRNALeu-like gene product which would recognize the UUA codon. Here we show that phenotypic expression of three disparate genes (carB, lacZ, and ampC) containing TTA codons depends strongly 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. 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. For hyg, evidence is presented that the UUA codon is probably being translated by a tRNA with an imperfectly matched anticodon, giving very low levels of gene product but relatively high resistance to hygromycin. It is proposed that TTA codons may be generally absent from genes expressed during vegetative growth and from the structural genes for differentiation and antibiotic production but present in some regulatory and resistance genes associated with the latter processes. The codon may therefore play a role in developmental regulation.