Chemical and biological characterization of two FK506 analogs produced by targeted gene disruption in Streptomyces sp. MA6548.
Two genetically engineered mutant strains of Streptomyces sp. MA6548 produced two FK506 analogs, 9-deoxo-31-O-demethylFK506 and 31-O-demethylFK506. The structures were determined by a combination of NMR and mass spectrometry. These compounds exhibited immunosuppressive and antifungal activities, albeit reduced, compared to FK506. Both compounds contain a free hydroxyl group at C-31 for the synthesis of novel FK506 derivatives.
Shafiee
A
A
Department of Natural Products Drug Discovery, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Motamedi
H
H
Dumont
F J
FJ
Arison
B H
BH
Miller
R R
RR
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D001234:Aspergillus niger / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005285:Fermentation; D005818:Genetic Engineering / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
C107029:9-deoxo-31-O-demethyl-FK506; D000935:Antifungal Agents; D007166:Immunosuppressive Agents; C107028:31-O-demethyl-FK506; D016559:Tacrolimus