Biosynthesis of formycin. Incorporation and distribution of 13C-, 14C-, and 15N-labeled compounds into formycin.

Identification and Characterization of Enzymes Catalyzing Pyrazolopyrimidine Formation in the Biosynthesis of Formycin A

“…Feeding experiments in N. interforma showed that the ribosyl moiety of formycin A is derived directly from ribose likely via an intermediary produced from phosphoribosyl pyrophosphate (PRPP, 3 ) . However, the N3 and N8 nitrogen centers of formycin A originate from the ε-amino group of l -lysine ( 5 ) . Importantly, l -glutamate ( 4 ) was found to be asymmetrically incorporated into formycin A such that the C6, C5, C4, and C9 carbons of formycin A are derived from the C1, C2, C3, and C4 carbons of glutamate (see Figure ).…”

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

“…The [14C]-and [13C]acetate incorporation data presented here, together with the report by Buchanan et al (1980c), show that the biosynthesis of the aglycon of pyrazofurin proceeds via the incorporation of glutamate or the conversion of acetate to glutamate followed by the incorporation into the amide carbon and C-5, C-4, and C-3. The present study, together with earlier reports from this laboratory (Elstner & Suhadolnik, 1971Elstner et al, 1973;Isono & Suhadolnik, 1977) and reports by Ochi et al (1979) and Buchanan et al (1980c), shows that glutamate (or acetate which is converted to glutamate) is the common asymmetric precursor for the biosynthesis of the four contiguous carbon atoms of the maleimide ring of showdomycin and the pyrazole ring of formycin and pyrazofurin and the three carbon atoms of the 1,3-oxazine-2,4-dione ring of oxazinomycin (Figure 2). This conclusion is based on the incorporation and percent distribution of (1) [3H], [14C], and [13C] glutamate into the aglycons of the C-nucleoside antibiotics by the Streptomyces-producing organisms and (2) 13C or 14C from [2-13C]-or [2-14C]acetate, following conversion to glutamate, into the carbon atoms of the aglycons of the four naturally occurring C-nucleoside antibiotics.…”

“…Similarly, the biosynthesis of the 1,3-oxazine-2,4-dione ring of the C-nucleoside, oxazinomycin, also occurs via the conversion of acetate to glutamate such that carbons 3, 4, and 5 of glutamate become carbons 6, 5, and 4 of oxazinomycin (Isono & Suhadolnik, 1977; Isono & Uzawa, 1977). Ochi et al (1979) have subsequently reported that [U-13C]glutamate was incorporated into the pyrazolopyrimidine ring of formycin. Reexamination of Ochi's 13C NMR data by Buchanan et al (1980c) shows that C-l through C-4 of glutamate serves as the four-carbon donor for carbons 6, 5, 4, and 9 of the aglycon of formycin.…”

Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis

“…Formycin A also exhibits antiviral activity against influenza virus A1 and human immunodeficiency virus type 1 . Although the biological functions of formycin A have been well-documented, little is known about how it is assembled in nature. , …”