Mode of action of the biotin antimetabolites actithiazic acid and alpha-methyldethiobiotin.
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.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology*; D001710:Biotin / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000494:pharmacology; D002208:Caproates / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D000900:Anti-Bacterial Agents; D000963:Antimetabolites; D002208:Caproates; D013844:Thiazoles; D053778:Thiazolidines; C010228:alpha-methyldethiobiotin; D001710:Biotin; C010250:mycobacidin