Abstract
Precursors singly and doubly labeled with stable isotopes can be used to study both the origins of antibiotic molecules and the mechanisms involved in their biosyntheses. In this review, the versatile methodology used for these approaches is discussed, using examples from the biosynthetic investigations of neomycin, ribostamycin, nybomycin and erythromycin and of two antibiotics containing the so–called m–C7N unit, pactamycin and gel–danamycin.
*The E. R. Squibb Lectures on Chemistry of Microbial Products presented at Waksman Institute of Microbiology, Rutgers University, New Brunswick, N.J. March 16, 17, 1983.
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References
Gottlieb, D. and Shaw, P.D. (eds). 1967. Antibiotics. Volume II: Biosynthesis, Springer: Berlin.
Corcoran, J.W. (ed). 1981. Antibiotics. Volume IV: Biosynthesis, Springer: Berlin.
McInnes, A.G., Walter, J.A., Wright, J.L.C. and Vining, L.C. 1976. pp. 123–178. 13C NMR biosynthetic studies. In: Topics in Carbon-13 NMR Spectroscopy, Vol. 2 G. C. Levy (ed), Wiley, New York.
Caprioli, R.M. 1972. pp. 735–776. Use of Stable Isotopes. In: Biochemical Applications of Mass Spectrometry, G. R. Waller (ed), Wiley, New York. Caprioli, R. M., Bier, D. M. 1980. Use of stable isotopes. In: Biochemical Applications of Mass Spectrometry, First Supplementary Volume, G. R. Waller and O. C. Dermer (eds), Wiley, New York.
Rinehart, K.L., Jr., Malik, J.M., Nystrom, R.F., Stroshane, R.M., Truitt, S.T., Taniguchi, M., Rolls, J.P., Haak, W.J. and Ruff, B.A. 1974. Biosynthetic incorporation of [1-13C]glucosamine and [1-13C]glucose into neomycin. J. Am. Chem. Soc. 96: 2263–2265.
Rinehart, K.L., Jr., 1979. Biosynthesis and mutasynthesis of aminocyclitol antibiotics. Jpn. J. Antibiot. 32, Suppl.: S32–S-46.
Kakinuma, K., Ogawa, Y., Sasaki, T., Seto, H. and Ōtake, N. 1981. Stereochemistry of ribostamycin biosynthesis. An application of 2H NMR spectroscopy. J. Am. Chem. Soc. 103: 5614–5616.
Nadzan, A.M., Rinehart, K.L., Jr., 1976. Nybomycin. VIII. Biosynthetic origin of the central ring carbons studied by 13C-labeled substrates. J. Am. Chem. Soc. 98: 5012–5014.
Nadzan, A.M., Rinehart, K.L., Jr., 1977. Nybomycin. IX. Synthetic and biosynthetic incorporation of 15N as a means of assigning the 13C nuclear magnetic resonance spectrum of nybomycin. J. Am. Chem. Soc. 99: 4647–4654.
Cane, D.E., Hasler, H., Liang, T.-C. 1981. Macrolide biosynthesis. Origin of the oxygen atoms in the erythromycins. J. Am. Chem. Soc. 103: 5960–5962.
Vederas, J.C. 1980. Structural dependence of 18O isotope shifts in 13C NMR spectra. J. Am. Chem. Soc. 102: 374–376.
Weller, D.D., Rinehart, K.L., Jr. 1978. Biosynthesis of the antitumor antibiotic pactamycin. A methionine-derived ethyl group and a C7N unit. J. Am. Chem. Soc. 100: 6757–6760.
Richards, J.H., Hendrickson, J.B. 1964. The Biosynthesis of Steroids, Terpenes, and Acetogenins, W. A. Benjamin, New York.
Walker, J.B. 1971. Enzymatic reactions involved in streptomycin biosynthesis and metabolism. Lloydia 34: 363–371.
Lederer, E. 1969. Some problems concerning biological C-alkylation reactions and phytosterol biosynthesis. Q. Rev. Chem. Soc. 23: 453–481.
Rinehart, K.L., Jr., Potgieter, M., Jin, W.-Z., Pearce, C.J., Wright, D.A., Wright, J.L.C., Walter, J.A. and McInnes, A.G. 1982. pp. 171–184. Biosynthetic studies on antibiotics employing stable isotopes. In: Proc. Intl. Conf. Trends Antibiot. Res., U. Umezawa, A. L. Demain, T. Hata, and C. R. Hutchinson (eds), Jpn. Antibiot. Res. Assoc, Tokyo.
Milavetz, B., Kakinuma, K., Rinehart, K.L., Jr., Rolls, J.P. and Haak, W.J. 1973. Carbon-13 magnetic resonance spectroscopy and the biosynthesis of streptovaricin. J. Am. Chem. Soc. 95: 5793–5795.
White, R.J., Martinelli, E. 1974. Ansamycin biogenesis: incorporation of [1-13C]glucose and [1-13C]glycerate into the chromophore of rifamycin S. FEES Lett. 49: 233–236.
Ghisalba, O., Roos, R., Schupp, T. and N¨esch, J. 1982. Transformation of rifamycin S into rifamycins B and L. A revision of the current biosynthetic hypothesis. J. Antibiot. 35: 74–80.
Kibby, J.J., McDonald, I.A. and Rickards, R.W. 1980. 3-Amino-5-hydroxybenzoic acid as a key intermediate in ansamycin and maytansinoid biosynthesis. J. Chem. Soc., Chem. Commun. 1980: 768–769.
Haber, A., Johnson, R.D. and Rinehart, K.L., Jr. 1977. Biosynthetic origin of the C2 units of geldanamycin and distribution of label from D-[6-13C]glucose. J. Am. Chem. Soc. 99: 3541–3544.
Rinehart, K.L., Jr., Potgieter, M. and Wright, D.A. 1982. Use of 13C-depleted glucose and homonuclear 13C-decoupling to identify the labeling pattern of the “m-C7N” unit of geldanamycin by [l3C6]glucose. J. Am. Chem. Soc. 104: 2649–2652.
Hornemann, U., Eggert, J.H., Honor, D.P. 1980. Role of D-[4-14C]Erythrose and [3-14C]pyruvate in the biosynthesis of the meta-C-C6-N unit of the mitomycin antibiotics in Streptomyces verticillatus. J. Chem. Soc., Chem. Commun. 1980: 11–13.
Rinehart, K.L., Jr., Potgieter, M., Delaware, D.L., Seto, H. 1981. Direct evidence from multiple 13C labeling and homonuclear decoupling for the labeling pattern by glucose of the m-aminobenzoyl (C7N) unit of pactamycin. J. Am. Chem. Soc. 103: 2099–2101.
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Rinehart, K. Newer Methods for Characterization of Antibiotics I: Stable Isotopes in the Study of Antibiotic Synthesis. Nat Biotechnol 1, 495–502 (1983). https://doi.org/10.1038/nbt0883-495
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DOI: https://doi.org/10.1038/nbt0883-495