Fig 1.

Proposed pathway of orotic acid metabolism in G. kaustophilus HTA426, based on the B. subtilis pathway. Orotic acid is metabolized to UMP by PyrE and PyrF. These enzymes also convert 5-FOA to 5-fluorouridine monophosphate, which is further metabolized to the toxic metabolite 5-fluorodeoxyuridine 5′-monophosphate. pyrR encodes an mRNA-binding attenuator that negatively regulates pyr expression by sensing UMP or UTP (34). UMP is also produced from uracil by uracil phosphoribosyltransferase.