Production of Guanosine-5′-Monophosphate and Inosine-5′-Monophosphate by Fermentation

A biotin-requiring coryneform bacterium which produces glutamic acid was mutated to adenine dependency. The adenine-requiring strain, which excreted insoine-5′-monophosphate (IMP), was further mutated to xanthine dependency. As expected, IMP was also excreted by this mutant. The mutant strain was reverted to xanthine independence in an attempt to obtain a culture with an altered IMP dehydrogenase which would be less sensitive to feedback inhibition by guanosine-5′-monophosphate (GMP). A revertant was obtained which produced GMP and IMP, each at 0.5 g per liter. The reversion to xanthine independence had resulted in a concomitant requirement for isoleucine, leucine, and valine. Further mutation to increased nutritional requirements led to culture MB-1802, which accumulated 1 g per liter each of GMP and IMP. Both nucleotides were isolated in pure form. The concentrations of GMP and IMP produced by MB-1802 were four times that of cytidylate, uridylate, or adenylate, indicating that the mechanism of GMP and IMP production was direct and not via ribonucleic acid breakdown.