The cyclohexane moiety of rapamycin is derived from shikimic acid inStreptomyces hygroscopicus

Although the addition of shikimic acid to the medium had no effect on the level of production of rapamycin byStreptomyces hygroscopicus,14C-shikimic acid was incorporated into rapamycin to a very high degree.13C-Shikimic acid was successfully prepared from 1-[13C]-glucose using a mutant ofKlebsiella pneumoniae, and used to label rapamycin. It was found that13C-shikimic acid was incorporated into the cyclohexane moiety of rapamycin, thereby establishing the shikimic acid pathway origin of the seven-carbon starter unit.