Abstract
Streptomyces antibioticus produces a family of actinomycin components which differ solely at the “imino acid” site of the molecule; however, new congeners of actinomycin are synthesized when cultures are supplemented with pipecolic acid (PA). The quantitative and qualitative nature of the actinomycins produced differed when cultures were incubated in the presence of either l-, d-, or racemic PA. In the presence of d-PA, the quantitative and qualitative nature of those actinomycins produced were similar to those produced in the absence of supplementation. By contrast, in the presence of l-PA or dl-PA new actinomycin components containing PA were synthesized at the expense of normally produced components. Also, the total amount of antibiotic produced decreased in response to increasing concentrations of exogenously supplied l-PA. This effect occurred whether or not d-PA was also added to cultures. Concentrations of l-PA greater than 125 μg/ml of medium resulted in no additional decrease in the amount of antibiotic produced. Although PA-containing actinomycins were formed as early as 6 h after the addition of 250 μg of l-PA per ml, it was not until 24 h postaddition that the relative percentages of actinomycin components produced approached a constant value. Evidence presented here indicated that the l-isomer of PA replaces l-proline in the pentapeptide of actinomycin.
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- BROCKMANN H., PFENNIG N. Die Gewinnung reiner Actinomycine durch Gegenstromverteilung (V. Mitteil. über Actinomycin). Hoppe Seylers Z Physiol Chem. 1953;292(1-2):77–88. [PubMed] [Google Scholar]
- FARBER S., D'ANGIO G., EVANS A., MITUS A. Clinical studies on actinomycin D with special reference to Wilms' tumor in children. Ann N Y Acad Sci. 1960 Oct 5;89:421–425. doi: 10.1111/j.1749-6632.1960.tb20165.x. [DOI] [PubMed] [Google Scholar]
- Formica J. V., Katz E. Isolation, purification, and characterization of pipecolic acid-containing actinomycins, Pip 2, Pip 1 , and Pip 1 . J Biol Chem. 1973 Mar 25;248(6):2066–2071. [PubMed] [Google Scholar]
- Formica J. V., Shatkin A. J., Katz E. Actinomycin analogues containing pipecolic acid: relationship of structure to biological activity. J Bacteriol. 1968 Jun;95(6):2139–2150. doi: 10.1128/jb.95.6.2139-2150.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GOSS W. A., KATZ E. Actinomycin formation by Streptomyces cultures. Appl Microbiol. 1957 Mar;5(2):95–102. doi: 10.1128/am.5.2.95-102.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goss W. A., Katz E., Waksman S. A. CHANGES IN THE COMPOSITION OF AN ACTINOMYCIN COMPLEX DURING GROWTH OF A STREPTOMYCES CULTURE. Proc Natl Acad Sci U S A. 1956 Jan;42(1):10–12. doi: 10.1073/pnas.42.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KATZ E. Biogenesis of the actinomycins. Ann N Y Acad Sci. 1960 Oct 5;89:304–322. doi: 10.1111/j.1749-6632.1960.tb20154.x. [DOI] [PubMed] [Google Scholar]
- KATZ E., GOSS W. A. Controlled biosynthesis of actinomycin with sarcosine. Biochem J. 1959 Nov;73:458–465. doi: 10.1042/bj0730458. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KATZ E., GOSS W. A. Influence of amino-acids of actinomycin biosynthesis. Nature. 1958 Dec 13;182(4650):1668–1669. doi: 10.1038/1821668b0. [DOI] [PubMed] [Google Scholar]
- KATZ E. Influence of valine, isoleucine, and related compounds on actinomycin synthesis. J Biol Chem. 1960 Apr;235:1090–1094. [PubMed] [Google Scholar]
- KATZ E., WEISSBACH H. Incorporation of C14-labeled amino acids into actinomycin and protein by Streptomyces antibioticus. J Biol Chem. 1963 Feb;238:666–675. [PubMed] [Google Scholar]
- ROSS G. T., STOLBACH L. L., HERTZ R. Actinomycin D in the treatment of methotrexate-resistant trophoblastic disease in women. Cancer Res. 1962 Sep;22:1015–1017. [PubMed] [Google Scholar]
- SCHWEET R. S. The quantitative determination of proline and pipecolic acid with ninhydrin. J Biol Chem. 1954 Jun;208(2):603–613. [PubMed] [Google Scholar]
- TROLL W., LINDSLEY J. A photometric method for the determination of proline. J Biol Chem. 1955 Aug;215(2):655–660. [PubMed] [Google Scholar]