Probing the Role of <i>N</i>-Acetyl-glutamyl 5-Phosphate, an Acyl Phosphate, in the Construction of the Azabicycle Moiety of the Azinomycins
作者:Keshav K. Nepal、Rachel P. Lee、Yohannes H. Rezenom、Coran M. H. Watanabe
DOI:10.1021/acs.biochem.5b00711
日期:2015.7.28
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.
阿齐霉素是由土壤细菌Streptomyces sahachiroi产生的强效抗肿瘤药物,含有新型氮丙啶[1,2-a]吡咯烷核心,其合成至少涉及14个步骤。本研究首次报道了由阿齐霉素生物合成基因簇编码的两个酶对N-乙酰谷氨酰胺半醛形成的重组。该反应通过形成酰基磷酸,并建立N-乙酰谷氨酰5-磷酸和N-乙酰谷氨酰胺半醛作为氮丙啶[1,2-a]吡咯烷部分复杂生物合成的中间体。