Mode of action of alpha-dehydrobiotin, a biotin analogue.
Alpha-Dehydrobiotin, like biotin, represses coordinately the 7,8-diaminopelargonic acid aminotransferase and the dethiobiotin synthetase enzymes that are encoded on the l and r strands, respectively, of the bioA operon. The rate of synthesis for both enzymes is inhibited about 80% in the presence of alpha-dehydrobiotin. Homobiotin and alpha-methylbiotin are less effective than alpha-dehydrobiotin in repressing the synthesis of the two enzymes. The selective repression of transcription from l and by alpha-dehydrobiotin and homobiotin, previously reported in hybridization experiments, is not observed at the enzyme level. A combination of equal concentrations of biotin and alpha-dehydrobiotin which was reported to enhance selectively the level of messenger ribonucleic acid transcribed from the l strand does not increase the rate of synthesis of the aminotransferase enzyme. Instead, the enzymes encoded on both strands are essentially completely inhibited as with biotin alone. Strain differences have been ruled out to account for the different results obtained by the two methodologies. Our evidence would suggest that alpha-dehydrobiotin acts like biotin, presumably as the co-repressor, in the repression of the bioA operon. The low rates of enzyme synthesis observed in the presence of the biotin analogue is the result of incomplete repression due to a lower affinity of either the analogue for the repressor or of the co-repressor/repressor complex for the operator. While our evidence would support the concept of a two promoter/operator complex, both would have to respond equally to biotin and its analogues. The evidence, however, does not rule out other possible alternative models for the regulation of the biotin operon.
D000596:Amino Acids; D001710:Biotin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019731:Carbon-Nitrogen Ligases; D004794:Enzyme Repression / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology*; D005227:Fatty Acids; D006824:Hybridization, Genetic; D007651:Keto Acids; D007700:Kinetics; D008025:Ligases / Q000096:biosynthesis*; D009154:Mutation; D009876:Operon / Q000187:drug effects*; D012436:S-Adenosylmethionine; D000637:Transaminases / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects
D000596:Amino Acids; D005227:Fatty Acids; D007651:Keto Acids; C010437:alpha-dehydrobiotin; D001710:Biotin; D012436:S-Adenosylmethionine; C020029:7,8-diaminopelargonic acid aminotransferase; D000637:Transaminases; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C020024:dethiobiotin synthetase