Action of azaserine on Escherichia coli.

Azaserine (O-diazoacetyl-L-serine) was first isolated from a crude broth filtrate of Streptomyces fragilis and found to possess marked antitumor activity (Ehrlich et al., 1954; Bartz et al., 1954; Stock et al., 1954). The chemical synthesis of this compound was reported immediately thereafter; the synthetic O-diazoacetyl-L-serine was found to be identical in all physical, chemical, and biological properties with the antibiotic azaserine (Moore et al., 1954). A comparison of the D and L isomers of O-diazoacetylserine demonstrated that the inhibitory activity resides in the isomer that contains L-serine (Nicolaides et al., 1954; Stock et al., 1954). The ability of azaserine to interfere with a number of biochemical events in various biological systems suggests that the antibiotic may disrupt one or more fundamental metabolic processes (Maxwell and Nickel, 1954; Coffey et al., 1954; Halvorson, 1954; Gots and Golub, 1956b; Dagg and Karnofsky, 1955; Barker et al., 1956). One of the biosynthetic steps which appears to be most sensitive to azaserine inhibition is the synthesis of purines. In both an avian liver system (Levenberg et al., 1957) and a bacterial system (Tomisek et al., 1956) a marked inhibition by azaserine of the amidination of (a-N-formyl)-glycinamide ribotide, a purine precursor, has been demonstrated. Further studies have revealed that the inhibitory action of azaserine in these systems appears to be on the utilization of the amide-N of glutamine as the source of nitrogen atom three of the purine nucleus; the competitive nature of the inhibition has, thus far, been established only for the avian liver system. The purpose of the present studies was to investigate some of the effects that are produced