Fig. 1
From: The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD
The enzymatic routes to synthesize 10-CHO-THF in different organisms. In E. coli, 10-CHO-THF is synthesized by FolD, while in several other bacteria such as Streptococci, 10-CHO-THF can be produced via an alternative enzyme named Fhs. In humans, there are different enzymes in the cytoplasm and the mitochondrion. In the cytoplasm, MTHFD1, which is a tri-functional enzyme, exerts FolD-DH, FolD-CYH and Fhs functions. In the mitochondrion, while MTHFD2 and MTHFD2L have FolD functions, MTHFD1L plays the same role as Fhs. The chemical structure of FolD inhibitor carolacton is shown in the centre
