Screening for new antifolates of microbial origin and a new antifolate AM-8402.

A screening method was established for new specific inhibitors of folate metabolism. Culture broths of soil isolates were selected based on relative microbial activity. A culture, to be retained, must be active against Enterococcus faecium grown in a medium which contains a limited amount of pteroic acid but lacks activity against the microorganism grown in a medium supplemented with thymidine. By this screening method, three new antibiotics, diazaquinomycins A and B and AM-8402 were selected from eight thousand soil isolates. The isolation and structures of diazaquinomycins have been reported. AM-8402 is a new antifolate active against Gram-positive bacteria and mycoplasmas. It consists of a nanaomycin D moiety as chromophore and a deoxysugar and is structurally related to medermycin.

[1]  S. Ōmura,et al.  Diazaquinomycin A, a new antifolate antibiotic, inhibits thymidylate synthase. , 1985, The Journal of antibiotics.

[2]  H. Sano,et al.  The structures of diazaquinomycins a and b, new antibiotic metabolites , 1983 .

[3]  H. Naganawa,et al.  VANOXONIN, A NEW INHIBITOR OF THYMIDYLATE SYNTHETASE , 1983 .

[4]  I. Rollo.  Inhibitors of Dihydrofolate Reductase as Antiprotozoal Agents , 1983 .

[5]  G. Hitchings.  Functions of Tetrahydrofolate and the Role of Dihydrofolate Reductase in Cellular Metabolism , 1983 .

[6]  H. Naganawa,et al.  Vanoxonin, a new inhibitor of thymidylate synthetase. , 1983, The Journal of antibiotics.

[7]  G. Brown,et al.  Biosynthesis of riboflavin, folic acid, thiamine, and pantothenic acid. , 2006, Advances in enzymology and related areas of molecular biology.

[8]  S. Ōmura,et al.  OM-704 A, a new antibiotic active against gram-positive bacteria produced by Streptomyces sp. , 1982, The Journal of antibiotics.

[9]  P. Danenberg.  Thymidylate synthetase - a target enzyme in cancer chemotherapy. , 1977, Biochimica et biophysica acta.

[10]  K. Hasuda,et al.  A new antibiotic, medermycin. , 1976, The Journal of antibiotics.

[11]  S. Ōmura,et al.  Isolation and structure of nanaomycin D, an enantiomer of the antibiotic kalafungin , 1976 .

[12]  M. Friedkin,et al.  Inhibition of thymidylate synthetase and dihydrofolate reductase by naturally occurring oligoglutamate derivatives of folic acid. , 1975, The Journal of biological chemistry.

[13]  D. Pruess,et al.  Antimetabolites from microorganisms. , 1974, Advances in applied microbiology.

[14]  S. Esumi,et al.  The structure of minimycin, a novel carbon-linked nucleoside antibiotic related to -pseudouridine. , 1972, The Journal of antibiotics.

[15]  O. Kawaguchi,et al.  Minimycin, a new antibiotic. , 1972, The Journal of antibiotics.

[16]  T. Okazaki,et al.  Oxazinomycin, a new carbon-linked nucleoside antibiotic. , 1971, The Journal of antibiotics.

[17]  E. Olson,et al.  Tirandamycin. I. Structure assignment. , 1971, Journal of the American Chemical Society.

[18]  C. E. Meyer.  Tirandamycin, a new antibiotic isolation and characterization. , 1971, The Journal of antibiotics.

[19]  F. Reusser.  Tirandamycin: Inhibition of Ribonucleic Acid Polymerase , 1970, Infection and immunity.

[20]  R. K. Robins,et al.  The structure of showdomycin, a novel carbon-linked nucleoside antibiotic related to uridine. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[21]  G. Hitchings,et al.  Inhibition of folate biosynthesis and function as a basis for chemotherapy. , 1965, Advances in enzymology and related areas of molecular biology.

[22]  Y. Tanaka,et al.  SHOWDOMYCIN, A NEW ANTIBIOTIC FROM A STREPTOMYCES SP. , 1964, The Journal of antibiotics.

[23]  W. C. Werkheiser.  THE BIOCHEMICAL, CELLULAR, AND PHARMACOLOGICAL ACTION AND EFFECTS OF THE FOLIC ACID ANTAGONISTS. , 1963, Cancer research.

[24]  G. Brown,et al.  The biosynthesis of folic acid. II. Inhibition by sulfonamides. , 1962, The Journal of biological chemistry.