Nogalamycin

Nogalamycin is an anthracycline antibiotic produced by the soil bacteria Streptomyces nogalater. It has antitumor properties but it is also highly cardiotoxic. The less cardiotoxic semisynthetic analog menogaril was developed in the 1970s. Currently nogalamycin and menogaril are not used clinically.Anthracycline biosynthesis involves the construction of an aglycone core (by a type II polyketide synthase) to which one or more sugar residues are attached. Nogalamycin consists of three components: Each component is built separately and then ligated together by a two glycosyltransferases. All of the machinery associated with the biosynthesis of nogalamycin are located within the same biosynthetic gene cluster of S. nogalater. The sugar moieties that are attached to nogalamycinone are produced from glucose-1-phosphate. Although the steps following dTDP-4-keto-6-deoxyglucose have not been confirmed in vitro, the high degree of sequence similarity with homologous enzymes from other organisms suggests that the mechanism proceeds as detailed at right. The following enzymes are involved in the biosynthesis of nogalamine and nogalose:The most noteworthy aspect of the structure of nogalamycin is the dual attachment of nogalamine both through O-glycosylation and also through a carbon-carbon bond at the C2 position of the nogalamycinone core, The following enzymes are involved in the final tailoring steps of nogalamycin. SnoN and snoT are genes in the nogalamycin gene cluster that are likely to catalyze the final hydroxylation: Nogalamycin is an anthracycline antibiotic produced by the soil bacteria Streptomyces nogalater. It has antitumor properties but it is also highly cardiotoxic. The less cardiotoxic semisynthetic analog menogaril was developed in the 1970s. Currently nogalamycin and menogaril are not used clinically.