THE CYCLOHEXANE MOIETY OF RAPAMYCIN IS DERIVED FROM SHIKIMIC ACID IN STREPTOMYCES-HYGROSCOPICUS

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