d -Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B

Significance Septacidin and its analogs are potential anticancer and pain-relief drugs. Hygromycin B is an anthelmintic agent practically used in swine and poultry farming. A common feature of these compounds is that they all have heptose moieties. Here we show that the heptoses of septacidin and hygromycin B are both derived from d -sedoheptulose-7-phosphate but are biosynthesized through different pathways. Septacidin producer, a gram-positive bacterium, shares the same ADP-heptose biosynthesis pathway with gram-negative bacterium lipopolysaccharide biosynthesis. These findings not only elucidate the biosynthesis mechanisms of septacidin and hygromycin B but enable opportunities for manipulation of their heptose moieties by combinatorial biosynthesis and for changing the structure of heptoses in gram-negative bacterium lipopolysaccharides.