<jats:title>ABSTRACT</jats:title> <jats:p> Nogalamycin is an anthracycline antibiotic produced by <jats:italic>Streptomyces nogalater</jats:italic> . Its aglycone has a unique stereochemistry (7S, 9S, 10R) compared to that of most other anthracyclines (7S, 9R, 10R). The gene <jats:italic>sno</jats:italic> aL, encoding a nogalonic acid methyl ester cyclase for nogalamycin, was used to generate nogalamycinone, demonstrating that the single cyclase dictates the C-9 stereochemistry of anthracyclines.