Actinomycins enzymatic synthesis

The enzymatic synthesis of the actinomycin chromophore also has been described (Weissbach and Katz, 1961 Katz and Weissbach 1962 Salzman, Weissbach and Katz, unpublished results). An enzyme, designated phenoxa-zinone synthetase, was obtained from sonic extracts of S. antihioticus and was shown to catalyze the oxidative condensation of o-aminophenols to the corresponding phenoxazinone. When 3-hydroxy-4-methylanthranilic acid (4MHAA) was used as substrate, actinocin was synthesized. The enzyme has been purified approximately 25- to 30-fold from sonic or French pressure cell extracts of the organism by means of standard protein fractionation procedures (ammonium... 

Actinomycin D is remarkably specific in inhibiting the synthesis of ribosomal RNA (DNA-primed) without any effect on the synthesis of DNA (Reich et al,y 1962). Use of radioactive actinomycin showed that it was covalently bound to the guanine of the DNA starter, and did not combine with any other cell component at concentrations that block RNA synthesis. The phenoxazine nucleus intercalates into DNA near to a G-C pair, and the peptide portions project into the minor groove (Muller and Crothers, 1968) (for more on intercalation see Section 10.3b). Whereas the action of the aminoacridines is sensitive to magnesium ions and insensitive to urea, precisely the reverse is true of actinomycin. Again, proflavine prevents the enzymatic synthesis of guanine-free polynycleotides, but actinomycin does not. 

Jones GH. Actinomycin synthesis in Streptomyces antibioticus Enzymatic conversion of 3-hydroxyanthranilic acid to 4.methyl 3 hydroxvanihranilic acid. J Bacteriol 1987 169 5575-5 578. 

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