Biological studies of amiclenomycin.
The action of amiclenomycin (AM) in inhibiting growth of microorganisms is specific against mycobacteria in vitro, but the antibiotic does not show a therapeutic effect against tubercle bacilli in vivo. The action of AM is reversed by biotin, desthiobiotin (DTB) and 7,8-diaminopelargonic acid (DAPA), but not by 7-keto-8-aminopelargonic acid (KAPA), pimelic acid and glutaric acid. In the presence of AM, cultures of Mycobacterium smegmatis and Bacillus sphaericus accumulated KAPA, whereas the formation of DTB decreased. Therefore, AM is thought to inhibit KAPA-DAPA transamination in biotin biosynthesis. In M. smegmatic and B. sphaericus the conversions of KAPA to DAPA and of DTB to biotin were rate limiting in biotin synthesis. Accordingly, the synergistic antibiotic activity of AM, inhibiting the former, and actithiazic acid, inhibiting the latter reaction, would be simply explained.
D000599:Amino Acids, Diamino / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001407:Bacillus / Q000187:drug effects; D001710:Biotin / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology; D002208:Caproates / Q000494:pharmacology; D003514:Cyclohexylamines / Q000494:pharmacology; D004357:Drug Synergism; D005227:Fatty Acids / Q000494:pharmacology; D005977:Glutarates / Q000494:pharmacology; D051379:Mice; D009161:Mycobacterium / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010867:Pimelic Acids / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000599:Amino Acids, Diamino; D000613:Aminobutyrates; D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D002208:Caproates; D003514:Cyclohexylamines; D005227:Fatty Acids; D005977:Glutarates; D010867:Pimelic Acids; D013844:Thiazoles; D001710:Biotin