Flavin-dependent thymidylate synthases (FDTS) catalyze the production of dTMP from dUMP and N 5 ,N 10 -methylene-5,6,7,8-tetrahydrofolate (CH2H4 folate). In contrast to human and other classical thymidylate synth-ases, the activity of FDTS depends on a FAD coenzyme, and its catalytic mechanism is very different.