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