Isolation and Characterization of Pre‐rapamycin, the First Macrocyclic Intermediate in the Biosynthesis of the Immunosuppressant Rapamycin by S. hygroscopicus

It's a rap: A double recombination strategy has been utilized to uncover the biosynthetic route to the key intermediate in the formation of rapamycin. Removal of a section of the rapamycin gene cluster from Streptomyces hygroscopicus produced a strain that generated no rapamycin. Gene complementation proved, surprisingly, that the accumulation of this previously elusive intermediate pre-rapamycin (1) depended on the presence of the gene rapK.