Nucleoside Antibiotics. Asymmetric Incorporation of Glutamic Acid and Acetate into the Maleimide Ring of Showdomycin by Streptomyces showdoensis

Carbon-14 from [1-14C]acetate, [2- and 5-14C]-glutamate, and [5-14C]a-ketoglutarate, but not [1-14C]a-keto-glutarate, resides in the carbonyl carbons of the maleimide ring. Degradation of the maleimide ring of showdomycin showed that all of the 14C from the [1-14C]acetate or [5-14C]-glutamate resides in C-5 of showdomycin while all of the 14C from [2-14C]glutamate resides in C-2 of showdomycin. Radioactivity from [2,3-14C]succinate, [2,3-14C]fumarate, and [2-14C]acetate was found in all four carbons of the maleimide ring of showdomycin. Apparently the Krebs cycle and the malic enzyme in Streptomyces showdoensis function in the conversion of fumarate and succinate to showdomycin. Further proof that C-4 of glutamate or a-ketoglutarate forms the carbon-carbon bond with D-ribose was obtained in an experiment with [5-14C,4-3H]glutamate. While 14C is incorporated into the maleimide ring all of the tritium is lost. Therefore, the four-carbon maleimide ring arising from C-2 to C-5 of a-ketoglutarate must be an asymmetrical unit when condensation occurs with D-ribose to form showdomycin.