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. 1982 Jan;21(1):5–10. doi: 10.1128/aac.21.1.5

Mode of action of the biotin antimetabolites actithiazic acid and alpha-methyldethiobiotin.

M A Eisenberg, S C Hsiung
PMCID: PMC181820  PMID: 7044300

Abstract

Actithiazic acid and alpha-methyldethiobiotin inhibited the conversion of dethiobiotin to biotin resting-cell suspensions of Escherichia coli. The concentrations which effected 50% inhibition were 0.45 and 1.1 microM for actithiazic acid and alpha-methyldethiobiotin, respectively. Cells grown in low concentrations of the two biotin antimetabolites showed derepression of the biotin A operon, as evidenced by the enhanced levels of the enzymes 7,8-diaminopelargonic acid aminotransferase and dethiobiotin synthetase. Derepression was not due to any direct regulatory effect of the antibiotics but was the consequence of the inhibition of the biotin synthetase enzyme; this inhibition prevented the intracellular concentration of biotin from reaching the levels required for normal regulation of the biotin A operon.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CLARK R. K., Jr, SCHENCK J. R. Actithiazic acid. III. The synthesis of DL-actithiazic acid, derivatives and homologs. Arch Biochem Biophys. 1952 Oct;40(2):270–276. doi: 10.1016/0003-9861(52)90111-2. [DOI] [PubMed] [Google Scholar]
  2. DHYSE F. G., HERTZ R. The effects of actithiazic acid on egg white-induced biotin deficiency and upon the microbial formation of biotin vitamers in the rat. Arch Biochem Biophys. 1958 Mar;74(1):7–16. doi: 10.1016/0003-9861(58)90194-2. [DOI] [PubMed] [Google Scholar]
  3. Eisenberg M. A. Biotin: biogenesis, transport, and their regulation. Adv Enzymol Relat Areas Mol Biol. 1973;38:317–372. doi: 10.1002/9780470122839.ch7. [DOI] [PubMed] [Google Scholar]
  4. Eisenberg M. A., Krell K. Dethiobiotin synthesis from 7,8-diaminolargonic acid in cell-free extracts of a biotin auxotroph of Escherichia coli K-12. J Biol Chem. 1969 Oct 25;244(20):5503–5509. [PubMed] [Google Scholar]
  5. Eisenberg M. A., Stoner G. L. Biosynthesis of 7,8-diaminopelargonic acid, a biotin intermediate, from 7-keto-8-aminopelargonic acid and S-adenosyl-L-methionine. J Bacteriol. 1971 Dec;108(3):1135–1140. doi: 10.1128/jb.108.3.1135-1140.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hanka L. J., Bergy M. E., Kelly R. B. Naturally occurring antimetabolite antibiotic related to biotin. Science. 1966 Dec 30;154(3757):1667–1668. doi: 10.1126/science.154.3757.1667. [DOI] [PubMed] [Google Scholar]
  7. Hanka L. J., Martin D. G., Reineke L. M. Two new antimetabolites of biotin: alpha-methyldethiobiotin and alpha-methylbiotin. Antimicrob Agents Chemother. 1972 Feb;1(2):135–138. doi: 10.1128/aac.1.2.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KAWASHIMA M., MIYAKE A., HEMMI T., FUJII S. Biochemical studies on acidomycin. III. Antibiotin activity of acidomycin and its related compounds. Pharm Bull. 1956 Feb;4(1):53–55. doi: 10.1248/cpb1953.4.53. [DOI] [PubMed] [Google Scholar]
  9. PITTILLO R. F., FOSTER J. W. Potentiation of inhibitor action through determination of reversing metabolites. J Bacteriol. 1954 Jan;67(1):53–57. doi: 10.1128/jb.67.1.53-57.1954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Prakash O., Eisenberg M. A. Active transport of biotin in Escherichia coli K-12. J Bacteriol. 1974 Nov;120(2):785–791. doi: 10.1128/jb.120.2.785-791.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. UMEZAWA H., OIKAWA K., OKAMI Y., MAEDA K. Thiazolidone antibiotic as an antimetabolite to biotin. J Bacteriol. 1953 Jul;66(1):118–119. doi: 10.1128/jb.66.1.118-119.1953. [DOI] [PMC free article] [PubMed] [Google Scholar]

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