Actinomycin synthesis

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. 

Fawaz F, Jones CH. Actinomycin synthesis in Streptomyces ontibiotinu Purification and properties of hydroxYanthranilate-4 mechylcransfetase. ] Biol Chem 1988 263 4602-4606. Jones GH. Combined purification of actinomycin synthetase I and 3-hydroxyanthranilic acid 4-methylttansferase from Streptamyces aruibi rmcus. ] Biol Chem 1993 268 6831-6834. Keller U, Schlumbohm W. Purification and characterization of actinomycin synthetase I. a 4 methy -3-hydroxyanthranilic acid AMP ligase from Streptomjees chrysomallus. J Biol Chem 1992 267 11745-11752. 

Ochi K, Katz E. The possible involvement of a plasmid(s) in actinomycin synthesis by Streptomyces pflTvwiws and Speptomyces mtibiotiews. J Antibiot 1978 31 1143-1148-... 

Ochi K. Protoplast fusion permits high frequency transfer of a Streptomyces determinant which mediates actinomycin synthesis. J Bacteriol 1982 150 592-597. 

Ochi K. A rel mutation abolishes the enzyme induction needed for actinomycin synthesis by Streptomyces onobiccicus. Agric Biol Chem 1987 51 829-835. 

Katz has reported that D-valine inhibits actinomycin synthesis and suggested that L-valine is the precursor of the D-valine which may occur in the molecule at sites B and B. ... 

During inhibition of actinomycin synthesis by D-valine, it was noted that a substance accumulated in the medium which yielded D-valine after mild acid hydrolysis. The compound was isolated, crystallized and identified by NMR spectra as N-succinyl-D-valine by comparison with authentic material (B arch as et al., 1964). The relationship of N-succinyl-D-valine to the inhibition of actinomycin biosynthesis by D-valine is not entirely clear. The compound does not appear to inhibit actinomycin formation. The possibility exists that N-succinyl-D-valine is a normal metabolite in the biosynthesis of antibiotic D-valine from free L-valine. d-Valine, in high concentrations, might inhibit antibiotic formation by competition with L-valine for the succinylation reaction. 

Fig. 5. Reversal of a-methyl-DL-trypto-phan inhibition of actinomycin synthesis by L-tryptophan. 5. antibioticus was grown in the basal medium a-methyl-DL-trypto-phan (5 [xg/ml) was added 24 hours after inoculation and L-tr tophan (40 p.g/ml) was introduced at 48 hours, at which time the actinomycin titer in control flasks was 18 [xg/ml and in the a-methyltryptophan-treated flasks, 0 p.g/ml. The data presented represents the actinomycin synthesized during the 48 to 72-hour period...

A study of the relationship of actinomycin synthesis to growth and protein synthesis by S. antihioticus revealed that antibiotic synthesis generally follows active growth and protein synthesis by the organism (Katz, Pienta and Sivak,... 

Fig. 12. Mycelium formation and actinomycin synthesis by 5. antihioticus during incubation in glutamic acid medium. Mycelium was determined on a dry weight basis...

A number of other antibiotics in addition to chloramphenicol and puromycin have been examined to determine their action upon actinomycin and protein synthesis as well as the size of the intracellular amino acid pool (Katz and Weiss-BACH, 1962, 1963 Katz, Wise and Weissbach, 1965). Streptomycin, neomycin, tetracycline, and erythromycin, which have been shown in other systems to inhibit protein synthesis, have all been found to stimulate actinomycin synthesis (Table 12). In each case incorporation of C-label into cellular proteins of 5. anti-hioticus was inhibited extensively whereas the C-labeled pool was larger in the presence of the antibiotics. Vancomycin and penicillin, inhibitors of cell wall synthesis, and actinomycin, which has been shown to inhibit the DNA dependent RNA S5mthesis, had no influence on actinomycin synthesis by this organism. The addition of mitomycin also had no effect on antibiotic formation. 

Fig. 14. Influence of 3-methyl-DL-proline on actinomycin synthesis and growth by 5. antihioticus. The organism was incubated in glutamic acid medium for 24 hours in absence of analogue. Mycelial growth at time of 3-methylproline addition was...

Katz, E. Inhibition of actinomycin synthesis by D-valine. Nature 184, 1666 (1959). 

Katz, E. Influence of valine, isoleucine and related compounds on actinomycin synthesis. J. Biol. Chem. 235, 1090 (l960b). 

SiVAK, A., and E. Katz Biosynthesis of the actinomycin chromophore. Influence of a-, 4-, 5 and 6-methyl-DL-tryptophan on actinomycin synthesis. Biochim. et Biophys. Acta 62, 80 (1962). 

Weissbach, H., B. Redfield, V. Beaven, and E. Katz Actinomycin synthesis in washed cells of Streptomyces antibioticus, J. Biol. Chem. 240, 4377 (1965)-... 

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