MICROBIAL CONVERSION OF RAPAMYCIN

In order to obtain derivatives of rapamycin, a total of 28 bacterial a nd 72 fungal strains were screened for their ability to transform rapa mycin. In the course of this screening, the already known derivatives 39-o-demethylrapamycin, 27-o-demethylrapamycin, 16-o-demethylrapamycin , and the 40-o-phosphoric ester of rapamycin were detected and isolate d out of fermentations with Streptomyces rimosus ATCC 28893 or Thamnid ium elegans ATCC 8997. Biotransformation of rapamycin using Syncephala strum racemosus ATCC 1332B, Gliocladium deliquescens ATCC 10097, or Ba cillus subtilis ATCC 55060 yielded the conversion products 24-hydroxyr apamycin, secorapamycin A, B, and C, and 16-o-demethylsecorapamycin B. None of these derivatives exhibited a stronger immunosuppressive effe ct than the parent compound; however, in the case of 24-hydroxyrapamyc in and 40-o-phosphoric ester of rapamycin, a FKBP-binding affinity com parable to rapamycin was observed. (C) 1997 Elsevier Science Inc.