Probing the Role of <i>N</i>‑Acetyl-glutamyl 5‑Phosphate, an Acyl Phosphate, in the Construction of the Azabicycle Moiety of the Azinomycins

The azinomycins are potent antitumor agents produced by the soil bacterium <i>Streptomyces sahachiroi</i> and contain a novel aziridino­[1,2-<i>a</i>]­pyrrolidine core; its synthesis involves at least 14 steps. This study reports the first reconstitution of <i>N</i>-acetylglutamine semialdehyde formation by two enzymes encoded in the azinomycin biosynthetic gene cluster. The reaction proceeds through the formation of an acylphosphate and establishes <i>N</i>-acetyl-glutamyl 5-phosphate and <i>N</i>-acetylglutamine semialdehyde as intermediates in the complex biosynthesis of the aziridino­[1,2-<i>a</i>]­pyrrolidine moiety