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, antitumor and selective immunosuppressive activities, too. This last effect was utilised by Roche-Syntex to develop a derivative of MPA to the immunosuppressive drug CellCept(R). In order to obtain novel derivatives of MPA with an enhanced activity, we applied bioconversion of MPA with various microorganisms. TLC with densitometric evaluation and HPLC methods were developed for measurement of MPA derivatives. In the course of the bioconversion of MPA by using various types of 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 transformations. 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 bioconversion were also determined. (C) 2001 Elsevier Science B.V. All rights reserved.