Microbiological transformation of mycophenolic acid

In our microbial screening program, we have isolated a fungal strain which produced mycophenolic acid (MPA). This compound is a selective inhibitor of guanine synthesis and, therefore, it has antibacterial, antiviral, antitum or and selective immunosuppressive activities, too. This last effect was ut ilised by Roche-Syntex to develop a derivative of MPA to the immunosuppress ive drug CellCept(R). In order to obtain novel derivatives of MPA with an enhanced activity, we a pplied bioconversion of MPA with various microorganisms. TLC with densitome tric evaluation and HPLC methods were developed for measurement of MPA deri vatives. In the course of the bioconversion of MPA by using various types o f microorganisms amidation of the carboxyl group, hydroxylation of the C-4- methyl group and formation of glycoside derivatives from the hydroxyl group located on C-7 were observed as the most frequently occurring transformati ons. The structures of bioconversion products were determined by UV, IR, H- 1 NMR, C-13 NMR and mass spectroscopic methods. The taxonomic features of cultures of the species applied in the bioconvers ion were also determined. (C) 2001 Elsevier Science B.V. All rights reserve d.