Mechanism of the antibiotic action of alpha-dehydrobiotin.
alpha-Dehydrobiotin, a naturally occurring biotin analogue, exhibits antibiotic properties [Hanka, L. J., Reineke, L. M., & Martin, D. G.(1969) J. Bacteriol. 100, 42--46]. It is shown in this paper that in addition to its activity as corepressor of the transcription of the biotin locus [Guha, A., Saturen, Y., & Szybalski, W. (1971) J. Mol. Biol. 56, 53--62] alpha-dehydrobiotin acts at the enzyme level. The synthesis of specifically tritiated alpha-dehydrobiotin has been achieved. By use of this labeled compound and a biotin-department strain of Escherichia coli, it has been demonstrated that alpha-dehydrobiotin can be linked covalently to proteins without further transformation. The fixation of biotin to apocarboxylases is inhibited irreversibly after preincubation with alpha-dehydrobiotin. This strongly supports the hypothesis that alpha-dehydrobiotin can be specifically linked to apocarboxylases in place of biotin and leads to carboxylases that are inactive. Thus, the antibiotic properties of alpha-dehydrobiotin would be partly due to the fact that it compete with biotin for the fixation on the apocarboxylases, producing irreversibly inactive enzymes.
D001692:Biological Transport / Q000187:drug effects; D001710:Biotin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005796:Genes; D007553:Isotope Labeling / Q000379:methods; D009154:Mutation; D014316:Tritium
D014316:Tritium; C010437:alpha-dehydrobiotin; D001710:Biotin