MICROBIAL SYNTHESIS OF 5-FLUOROURIDINE MONOPHOSPHATE AND 5-FLUORO-2'-DEOXYURIDINE MONOPHOSPHATE

A microbial nucleoside phosphotransferase reaction was applied for the conversion of 5-fluorouridine (FUR) and 5-fluoro-2'-deoxyuridine (FUd R) into the corresponding fluorinated nucleotide analogs on a preparat ive scale. Under optimized conditions using washed cells of Serratia m arcescens IFO 3046 and p-nitrophenyl phosphate as a phosphate donor, F UR and FUdR were converted to the phosphorylated form with conversion yields of 81.5% and 69.0%, respectively. Chemical and enzymatic analys es supported identification of the two fluorinated nucleotide products as 5-fluorouridine 5'-monophosphate (FUMP) and 5-fluoro-2-'deoxyuridi ne 5'-monophosphate (FdUMP). The phosphotransferase reaction product, FUMP, could be directly used for the successive synthesis of 5-fluorou ridine diphosphate galactose using air-dried cells of Candida saitoana IFO 0768.