1887

Abstract

Mutants of that are blocked in the synthesis of the phenoxazinone-containing antibiotic, actinomycin, were isolated by the ‘agar piece’ method (after ultra-violet irradiation or treatment with 8-methoxypsoralen plus near-ultraviolet light). Radio-labelling experiments in conjunction with paper, thin-layer and column chromatography revealed that 4-methyl-3-hydroxyanthranilic acid (MHA) is a major metabolite accumulated by these mutants. Studies and provided evidence that MHA is a precursor of the phenoxazinone chromophore, actinocin. Normally MHA does not accumulate during growth or antibiotic synthesis by the parental strains. Protoplasts derived from the mutant strain AM5 synthesized MHA in significant amounts. A scheme is proposed for the biosynthesis of actinomycin D that accounts for the accumulation of MHA by the mutants.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-111-1-121
1979-03-01
2021-05-17
Loading full text...

Full text loading...

/deliver/fulltext/micro/111/1/mic-111-1-121.html?itemId=/content/journal/micro/10.1099/00221287-111-1-121&mimeType=html&fmt=ahah

References

  1. ACHENBACH H., WORTH J. 1977; Michigazon, ein neues Phenoxazon aus Streptomyces michiganensis- Konstitutionsermittlung und Synthese. Chemische Berichte 110:12–22
    [Google Scholar]
  2. AHMAD F., MOAT A. G. 1966; Nicotinic acid biosynthesis in prototrophs and tryptophan auxotrophsof Saccharomyces cerevisiae.. Journal of Biological Chemistry 241:755–779
    [Google Scholar]
  3. BEADLE G. W., MITCHELL. H. K. 1947; Kynurenine as an intermediate in the formation of nicotinic acid from tryptophan by Neurospora.. Proceedings of the National Academy of Sciences of the United States of America 33:155–158
    [Google Scholar]
  4. BEAVEN V., BARCHA J., KATZ E., WEISSBACH H. 1967; KyStudies on the inhibition of actinomycin biosynthesis by D-valine.. Journal of Biological Chemistry 242:657–660
    [Google Scholar]
  5. BRAY G. A. 1960; A simple efficient liquid scintillator for counting aqueous solutions in a liquid scintillation counter.. Analytical Biochemistry 1:279–285
    [Google Scholar]
  6. BUTENANDT A. 1957; Uber Ommochrome, einenaturlicher Phenoxazon Farbstoff.. Angewandte Chemie 69:16–23
    [Google Scholar]
  7. BUTENANDT A., BECKMAN R. 1955; Uber Ommochrome VI. Mitteilung. Zur Genese von Rhodommatin und Ommatin C.. Zeitschrift fir physiologische Chemie 301:115–117
    [Google Scholar]
  8. BUTENANDT A., NEUBERT G. 1955; UbUber Ommochrome V. Mitteilung. Xanthommatin, ein Augenfarbstoff der Schmeissfliege Calliophoraerythrocephala. . Zeitschrijl fur physiologische Chemie 301:109–114
    [Google Scholar]
  9. BUTENANDT A., WEIDEL W., BECKER E. 1940; Kynurenin, als Augenpigment Bildung auslosendes Agens bei Insekten.. Naturwissenschaften 28:63–64
    [Google Scholar]
  10. BUTENANDT A., WEIDEL W., SCHLOSSBERGER H. 1949; 3-Oxykynurenine als Cnf-Genabhangiges Glied in intermediaren Tryptophan-Stoffwechsel.. Zeitschriji fur Natur forschung 4b:242–244
    [Google Scholar]
  11. CHAYKIN S. 1967; Nicotinamide coenzymes.. Annual Review of Biochemistry 36:149–170
    [Google Scholar]
  12. DELIćC V., HOPWOOD D.A., FRIEND E.J. 1970; Mutagenesis by N-methyl-N’-nitro-N-nitrosoguanidine (NTG) in Streptomyces coelicolor.. Mutation Research 9:167–182
    [Google Scholar]
  13. GALLO M., KATZ E. 1972; Regulation of secondary metabolite biosynthesis : catabolite repression of phenoxazinone synthase and actinomycin formation by glucose.. Journal of Bacteriology 109:659–667
    [Google Scholar]
  14. GERBER N . Phenoxazinones.In Handbook of Microbiology,. p. Laskin A. , Lechevalier. H. . Handbook of Microbiology vol. 111, Cleveland, Ohio :: CRC Press.;333 1973
    [Google Scholar]
  15. GOLUB E.E., WARD M.A., NISHIMURA J.S. 1969; Biosynthesis of the actinomycin chromophore: incorporation of 3-hydroxy-4-methylanthranilic acid into actinomycins by Streptomyces antibioticus.. Journal of Bacteriology 100:997–984
    [Google Scholar]
  16. GROVE D.C., RANDALL W.H. 1955; Assay Methods of Antibiotics, . Antibiotics Monograph New York:: Medical Encyclopedia.; No. 2,:35
    [Google Scholar]
  17. HITCHOCK M. J. M., KATZ E. 1978; Actinomycin biosynthesis by protoplasts derived from Streptomyces parvulus.. Antimicrobial Agents and Chemotherapy 13:104–114
    [Google Scholar]
  18. HOOK D. J., VINING L.C. 1973; Biosynthetic precursors of etamycin, a peptidolactone antibiotic from Streptomyces griseoviridus.. Canadian Journal of Biochemistry 51:1630–1637
    [Google Scholar]
  19. ICHIKAWA T., DATE M., ISHIKURA T., OZAKI A. 1971; Improvement of Kasugamycin-producing strain by the agar piece method and the prototrophic method.. Folia microbiologica 16:218–224
    [Google Scholar]
  20. KATZ E., DEMAIN A. 1977; The peptide antibiotics of Bacillus : chemistry, biogenesis and possible functions. Bacteriological Reviews 41:449–474
    [Google Scholar]
  21. KATZ E., DEMAIN A. 1977; The peptide antibiotics of Bacillus : chemistry, biogenesis and possible functions. Bacteriological Reviews 41:449–474
    [Google Scholar]
  22. KATZ E., WEISSBACH H. 1962; Biosynthesis of the actinomycin chromophore : enzymatic conversion of 4-methyl-3-hydroxyanthranilica cid to actinocin.. Journal of Biological Chemistry 237:882–886
    [Google Scholar]
  23. KATz, E., WEISSBACH H. 1963; Incorporation of Cle-labeled amino acids into actinomycin and protein by Streptomyces antibioticus.. Journal of Biological Chemistry 238:666–675
    [Google Scholar]
  24. KATZ E., WEISSBACH H. 1967; Studies on the cell-free synthesis of actinomycins.. Developments in Industrial Microbiology 8:67–87
    [Google Scholar]
  25. KELLER U., KLEINKAUF H. 1977; Studies of the biosynthesis of actinomycin in protoplasts from Streptomyces antibioticus.. Archives of Biochemistry and Biophysics 184:111–124
    [Google Scholar]
  26. KELLER A. 1948; Mutation in Streptomyces flaveolus induced by X-rays and ultraviolet light.. Journal of Bacteriology 56:457–465
    [Google Scholar]
  27. KRAMER J., CARTER G.G.,, ARRET B., WILNER J., WRIGHT W.W., KIRSCHBAUM A. 1968; Mutation in Streptomyces flaveolus induced by X-rays and ultraviolet light. Methods, Reports and Protocols, Part I. Washington:. National Center for Antibiotic and Insulin Analysis, U.S. Department of H.E.W.
    [Google Scholar]
  28. KREBS K.G., HEUSSER D., WIMMER H. Spray Reagents. In Stahl. E. Thin-Layer Chromatography pp. New York:: Springer-Verlag.;854–909 1969
    [Google Scholar]
  29. LINGENS F., VOLLPRECHT P. 1964; Zur Biosynthesedie Nicotinsaure in Streptomyceten, Algen, Phycomyceten und Hefe.. Zeitschrift fur physiologische Chemie 339:64–75
    [Google Scholar]
  30. LINGENS F., VOLLPRECHT P., GILDEMEISTER V. 1966; Zur Biosynthesedie Nicotinsaure in Streptomyceten, Algen, Phycomyceten und Hefe.. Biochemische Zeitschrgt 344:462–477
    [Google Scholar]
  31. LINZEN B. 1974; The tryptophan-ommochrome pathway in insects.. Advances in Insect Physiology 10:117–246
    [Google Scholar]
  32. MEIENHOFER J., ATHERTON E. 1973; Structureactivity relationships in the actinomycins.. Advances in Applied Microbiology 16:203–300
    [Google Scholar]
  33. PARADA J. L. 1975; Selective filtration in the isolation of independent clones of Streptomyces. Applied Microbiology 29:13–16
    [Google Scholar]
  34. SALZMAN L. H., WEISSBACH H., KATZ E. 1969; Enzymatic synthesis of actinocinylpeptides. Archives of Biochemistry and Biophysics 130:536–546
    [Google Scholar]
  35. TATUM E. L. 1939; Development of eye colors in Drosophila. Bacterial synthesis of Vf hormone.. Proceedings of the National Academy of Sciences of the United States of America 25:486–490
    [Google Scholar]
  36. TATUM E. L., HAAGEN-SMIT A. J. 1941; Identification of Drosophila V+ hormone of bacterial origin.. Journal of Biological Chemistry 140:575–580
    [Google Scholar]
  37. TOWNSEND M. E., WRIGHT, H. M., HOPWOOD D. A. 1971; Efficient mutagenesis by near ultraviolet light in the presence of 8-methoxypsoralen in S treptomyces.. Journal of Applied Bacteriology 34:799–801
    [Google Scholar]
  38. TROOST T., BROWN D., HITCHCOCK M., KATZ E. 1978; The role of primary metabolism in the biosynthesis of a secondary metabolite.. Bacteriological Proceedings 185
    [Google Scholar]
  39. WEISSBACH H., REDFIELD B., BEAVEN V., KATZ, E. 1965b; Actinomycin synthesis in washed cells of Streptomyces antibioticus. Journal of Biological Chemistry 240:4377–4381
    [Google Scholar]
  40. WILLIAMS W.K., KATZ E. 1977; Development of a chemically defined medium for the synthesis of actinomycin D by Streptomyces parvulus.. Antimicrobial Agents and Chemotherapy 11:281–290
    [Google Scholar]
  41. WILSON R. G., HENDERSON L.M. 1963; Tryptophan-niacin relationship in Xanthomonas pruni.. Journal of Bacteriology 85:221–229
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-111-1-121
Loading
/content/journal/micro/10.1099/00221287-111-1-121
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error