Actinomycins controlled biosynthesis

Actinomycin F, Actinomycin KS4 KS4. An antibiotic produced by cultures of actinomycin C-elaborat-ing strains of Streptomyces, such as Streptomyces BOP 476 (NRRL 2580) and Sirt-piomy r. chrysomaltus (NRRL 2250). Considered to be a derivative of actinomycin C2 amino acid analysis indicates that the prolines present in actinomycin C2 are substituted by sarcosine in actinomycin I, Production by controlled biosynthesis Schmidt-Kastner. Naturwiss. 43, 131 (1956) idem, Ann. N.Y. Acad. Set. 89, 199 (1960) Schmidt-Kastner, Hackmann, U.S. pat. 3,219,544 (1965 to Bayer). 

Kacr E, Goss WA. Controlled biosynthesis of actinomycin with sarcosine. Biochem J 1959 73 459-465. 

Controlled biosynthesis can be defined as the technique of predetermining the structure of a new antibiotic by furnishing specific chemical precursors to the antibiotic-producing microorganism (Woodruff and McDaniel, 1958). This technique has been successfully applied to the formation of modified forms of actinomycin. 

Schmidt-Kastner, G. The production of actinomycins by controlled biosynthesis The F actinomycins. Ann. N.Y. Acad. Sci. 89, 299 (i960). 

It is, however, not the only mechanism regulating enzyme amount. Experiments with actinomycin D (D 8.4.1), an inhibitor of transcription, revealed a considerable gap between the onset of transcription and the actual beginning of secondary product formation in dipicolinic acid biosynthesis (D 18) during bacterial sporulation. This suggests control of enzyme synthesis on the transcriptional and on one of the posttranscriptional levels. The bacteria probably have stable mRNA species whose translation offers a second level of control of the overall process. 

In most cases the mechanism by which nutrients control secondary metabolism is unknown. However, glucose and other rapidly used carbon sources repress the formation of iV-acetylkanamycin amidohydrolase, thought to be the final enzyme of kanamycin A biosynthesis (D 1.3) and phenoxazinone synthase, an enzyme required in actinomycin biosynthesis (D 8.4.1). 

Effect of actinomyin JD, cycloheximide, and azacytidine on de novo purine biosynthesis Table 2 illustrates that all three inhibitors, actinomycin D, cycloheximide, and azacytidine inhibit de novo purine biosynthesis as measured by the incorporation of -formate into total purines Labelling was for 2 hours, and the results are the average of three experiments Controls had between 25,000 and 30,000 cpm/10 cells Actinomycin D had no effect on Li vitro assayed PRPP amidotransferase or PRPP synthetase activities for cell pretreated for 2 hours with the drug ... 

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