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.
Biosynthesis
Anthracycline biosynthesis involves the construction of an aglycone core to which one or more sugar residues are attached. Nogalamycin consists of three components:- nogalamycinone, the aglycone core
- nogalose
- nogalamine
Nogalamycinone biosynthesis
The biosynthetic pathway towards the aglycone core of nogalamycin has been determined by a combination of bioinformatic analysis and cloning of individual components of the biosynthetic pathway. The biosynthetic route is similar to that of aklavinone, the sole difference being that the first acyl group that is loaded into the PKS is an acetate rather than a propionate. The following genes are involved in the biosynthesis of the core nogalamycinone species:snoa1 snoa2 snoa3 snoaD snoaE snoaM snoaB snoaC snoaL snoaF
Nogalamine and nogalose biosynthesis
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:snogJ snogK snogF snogH snogN snogI snogG snogC snogA snogX snogG2
Note that while much of the literature refers to the final, permethylated carbohydrate moiety as "nogalose", more recent data suggest that the nogalose moiety on nogalamycin is methylated after the nogalamycinone core has been glycosylated.