Glutamate as the common precursor for the aglycon of the naturally occurring C-nucleoside antibiotics.

ABSTRACT

Pyrazofurin is one of four naturally occurring C-nucleoside antibiotics; it is elaborated by Streptomyces candidus. The biosynthesis of the pyrazole ring of pyrazofurin has been studied by using 13C- and 14C-labeled acetate. Carbon-13 incorporation into pyrazofurin was observed by proton-decoupled 13C Fourier transform NMR spectroscopy. The incorporation of 14C from [1-14C]acetate was 0.7%. The enrichment of carbons 3, 4, and 5 of pyrazofurin from [2-13C]acetate by S. candidus confirms earlier findings that acetate is converted to glutamate by the combined action of the Krebs cycle and malic enzyme [Elstner, E. F., Suhadolnik, R. J., & Allerhand, A. (1973) J. Biol. Chem. 248, 5385]. Malic enzyme will give rise to [1,2-13C]acetate from [2-13C]acetate. The [1,2-13C]acetate is then converted to glutamate labeled with 13C in carbons 2--5. The 13C incorporation data indicate that carbons 1, 2, 3, and 4, but not 5, of glutamate serve as the four-carbon donor for the carboxamide carbon, C-5, C-4, and C-3, respectively, of the pyrazole ring of pyrazofurin.