Partial inhibition of protein synthesis accelerates the synthesis of porphyrin in heme-deficient mutants of Escherichia coli.
Mutants of Escherichia coli defective in the HemA protein grow extremely poorly as the result of heme deficiency. A novel hemA mutant was identified whose rate of growth was dramatically enhanced by addition to the medium of low concentrations of translational inhibitors, such as chloramphenicol and tetracycline. This mutant (H110) carries mutation at position 314 in the hemA gene, which resulted in diminished activity of the encoded protein. Restoration of growth of H110 upon addition of the drugs mentioned above was due to activation of the synthesis of porphyrin. However, this activation was not characteristic exclusively of cells with this mutant hemA gene since it was also observed in a heme-deficient strain bearing the wild-type hemA gene. The activation did not depend on the promoter activity of the hemA gene, as indicated by studies with fusion genes. It appears that partial inhibition of protein synthesis via inhibition of peptidyltransferase can promote the synthesis of porphyrin by providing an increased supply of glutamyl-tRNA for porphyrin synthesis. Glutamyl-tRNA is the common substrate for peptidyltransferase and HemA.
Nakayashiki
T
T
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
Nishimura
K
K
Tanaka
R
R
Inokuchi
H
H
D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002701:Chloramphenicol / Q000494:pharmacology; D003001:Cloning, Molecular; D017931:DNA Primers; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D005798:Genes, Bacterial; D005838:Genotype; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011166:Porphyrins / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013752:Tetracycline / Q000494:pharmacology; D001616:beta-Galactosidase / Q000096:biosynthesis
D017931:DNA Primers; D011166:Porphyrins; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D002701:Chloramphenicol; D000445:Aldehyde Oxidoreductases; C067282:glutamyl tRNA reductase; D001616:beta-Galactosidase; D013752:Tetracycline