CHENG YR, CHEN C, LIN F, HUANG J, PANDEY RC; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. F-2038.

Institute of Microbiology, State Pharmaceutical Administration of China and Fujian Province, Fuzhou, China.

BACKGROUND: Rapamycin (Sirolimus) produced by Streptomyces hygroscopicus ATCC 367817 is a powerful macrolide immunosuppressant, also with antitumor and antifungal activities. Rapamycin and FK506 catalyze protein folding and are supposed to mediate the immunosuppressive effects of rapamycin. However, we don't know the real functions on the presence of the FKBPs in bacteria. METHODS: S. hygroscopicus ATCC 367817 and its higher rapamycin producing mutants, mutant R27, R388 and R44 were studied. The production of rapamicin was monitored by HPLC. FKBPs were isolated and purified at 4 degrees C. The PPIase activity and the protein were determined. RESULTS: We found three poteins having relative molecular mass of about 15.5KD, 25KD and 52KD respectively from S. hygroscopicus ATCC 367817. Furthermore, the purified 15.5KD and 25KD proteins showed PPIase activities binding specificity with rapamycin. However, the purified 52KD protein showed no enzymatic activity. These findings indicated that the rapamycin-producing S. hygorscopicus ATCC 367817 contains FKBP12 and FKBP25. Surprisingly, all the higher rapamycin producing mutants in the experiments showed only two proteins having relative molecular mass of about 25KD and 52KD respectively, and no presence of a 15.5KD protein. Moreover, the purified protein which revealed a single homogeneous band with a 25KD molecular mass was significantly less than the FKBP25 from S. hygroscopicus ATCC 367817 and also the enzymatic activity was significantly less than that of the FKBP25 from strain ATCC 367817. CONCLUSIONS: The preliminary results reveal that there is a relevance between the production of rapamycin and the FKBPs (FKBP12 and/or FKBP25) from different rapamycin producing strains.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Bacterial Agents
• Immunosuppressive Agents
• Sirolimus
• Streptomyces
• Tacrolimus
• Tacrolimus Binding Protein 1A
• Tacrolimus Binding Proteins
• economics

Other ID:

• GWAIDS0028039

UI: 102267663

From Meeting Abstracts