Nutritional Studies on the Growth of the Rapamycin-Producing Streptomyces hygroscopicus

  • Kim, Wan-Seop (Diosynth RTP, Inc.,) ;
  • Davis, Sean (Emory University, School of Medicine) ;
  • Wong, Grace (University of Hawaii, School of Medicine) ;
  • Demain, Arnold-L. (Charles A. Dana Research Institute for Scientists Emeriti(R.I.S.E))
  • Published : 2003.08.01

Abstract

During our previous studies on the relationship between nutrient requirements of S. hygroscopicus C9 and rapamycin biosynthesis, we developed chemically-defined media containing among other nutrients, aspartic acid, arginine, histidine, or ammonium sulfate. However, these media (“Cheng et al. medium” and “Lee et al. medium”) showed very slow growth characterized by a very long lag phase of growth. In an attempt to develop a chemically-defined or semi-defined medium to support more rapid growth and increased cell production, we have carried out studies to shorten the lag phase. Of the various additives tested, vitamin-free casein acid hydrolysate was the most significant by shortening the lag phase by 2-3 days. Mixtures of amino acids failed to replace casein acid hydrolysate. The active principle passed through an ultrafilter with a molecular weight cutoff of 1,000 and thus may be a peptide. The present work has yielded a semi-defined medium which should be useful for further growth studies on S. hygroscopicus C9.

Keywords

References

  1. Appl. Microbiol. Biotechnol. v.43 Effect of amino acids on rapamycin biosynthesis by Streptomyces hygroscopicus Cheng,Y.R.;A.Fang;A.L.Demain https://doi.org/10.1007/BF00166931
  2. J. Indust. Microbiol. v.14 Phosphate, ammonium, magnesium and iron nutrition of Streptomyces hygroscopicus with respect to rapamycin biosynthesis Cheng,Y.R.;L.Hauck;A.L.Demain https://doi.org/10.1007/BF01569962
  3. J. Bacteriol. v.78 Role of fatty acids in the growth stimulation of Sarcina species by vitamin-free casein digests Demain,A.L.;D.Hendlin;J.A.Newkirk
  4. J. Indust. Microbiol. v.14 Carbon source nutrition of rapamycin biosynthesis in Streptomyces hygroscopicus Kojima,I.;Y.R.Cheng;V.Mohan;A.L.Demain https://doi.org/10.1007/BF01573954
  5. J. Indust. Microbiol. Biotechnol. v.19 Effect of nitrogen source on biosynthesis of rapamycin by Streptomyces hygroscopicus Lee,M.S.;I.Kojima;A.L.Demain https://doi.org/10.1038/sj.jim.2900434
  6. J. Nat. Prod. v.54 Incorporation of acetate, propionate, and methionine into rapamycin by streptomyces hygroscopicus Paiva,N.L.;A.L.Demain;M.F.Roberts https://doi.org/10.1021/np50073a015
  7. J. Indust. Microbiol. v.12 The cyclohexane moiety of rapamycin is derived from shikimic acid in Streptomyces hygroscopicus Paiva,N.L.;M.F.Roberts;A.L.Demain https://doi.org/10.1007/BF01569676
  8. J. Antibiot. v.28 Rapamycin(AY-22.989), a new antifungal antibiotic.Ⅱ, Fermentation, isolation and characterization Sehgal,S.N.;H.Baker;C.Venzina https://doi.org/10.7164/antibiotics.28.727
  9. Soc. Indust. Microbiol.(SIM) News v.41 Rapamycin: A new immunosuppressive macrolide Sehgal,S.N.;J.Y.Chang