Microbial Conversion Of Sirolimus

Sirolimus produced by Streptomyces hygroscopicus FC904 is a 36-membered macrolide immunosuppressant with antifungal, antiproliferative and antitumor activity. The structural modification of sirolimus has attracted great interest for its multifunctional effect and applied value. Several novel mTOR inhibitors such as RAD001, CCI-779 and AP23573 made by chemical synthesis have been used as coating for vascular stents to prevent restenosis of coronary arteries and are being developed into anticancer targeting drugs. Besides the chemical synthesis, microbial conversion is performed as an another approach for searching novel analogs of sirolimus. In this paper, it showed that different types of 66 culture were screened for the biotransformation of sirolimus and 15 strains of Micromonospora and 1 strain of Actinoplanes were found to be capable of transforming sirolimus. Micromonospora sp. FIM03-712 as a candidate was selected and classified as Micromonospora chersina. The conversion conditions of sirolimus by Micromonospora sp. FIM03-712 were explored. One conversion product, FJ900, from the broth of the strain was isolated and purified. By means of physico-chemical properties and spectral analyses such as HPLC, UV, IR, LC-MS and NMR, FJ900 was turned out to be identical with 14-deoxorapamycin. In comparation with sirolimus, FJ900 had less activity in antifungal and immunosuppressive actions. Whereas, the anticancer activity will be investigated further.