Effect of structural and stereochemical methylproline isomers on actinomycin biosynthesis.
The inhibitory effect of methylprolines on actinomycin biosynthesis by Streptomyces antibioticus was studied; the order of effectiveness was 3- >4- >5-methyl-dl-proline. Cis-3-methyl-dl-proline was 14 times more active than the trans isomer. It was also found that 4- and, possibly, 5-methylproline were incorporated into the actinomycin molecule. When 4-methylproline was present, three new actinomycins, representing 50 to 60% of the antibiotic mixture, were synthesized. Growth of the organism may be stimulated at concentrations (0.1 to 1.0 mug per ml) of 3-methylproline that inhibit antibiotic formation, thus providing additional evidence for a different mechanism of actinomycin synthesis from that of protein synthesis. Azetidine-2-carboxylic acid, piperdine-2-carboxylic acid, and hydroxyproline (but not sarcosine) reversed the inhibition due to 3-methylproline.
D002854:Chromatography, Paper; D003609:Dactinomycin / Q000032:analysis / Q000096:biosynthesis*; D004586:Electrophoresis; D011392:Proline / Q000096:biosynthesis / Q000494:pharmacology*; D013053:Spectrophotometry; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism; D014633:Valine / Q000096:biosynthesis
D003609:Dactinomycin; D011392:Proline; D014633:Valine