EC - Thymidylate synthase (FAD)

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IntEnz Enzyme Nomenclature


Accepted name:
thymidylate synthase (FAD)
Other names:
flavin dependent thymidylate synthase
Systematic name:
5,10-methylenetetrahydrofolate,FADH2:dUMP C-methyltransferase



Contains FAD. All thymidylate synthases catalyse a reductive methylation involving the transfer of the methylene group of 5,10-methylenetetrahydrofolate to the C5-position of dUMP and a two electron reduction of the methylene group to a methyl group. Unlike the classical thymidylate synthase, ThyA (EC, which uses folate as both a 1-carbon donor and a source of reducing equivalents, this enzyme uses a flavin coenzyme as a source of reducing equivalents, which are derived from NADPH.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
Gene Ontology: GO:0050797
UniProtKB/Swiss-Prot: (78) [show] [UniProt]


  1. Myllykallio, H., Lipowski, G., Leduc, D., Filee, J., Forterre, P., Liebl, U.
    An alternative flavin-dependent mechanism for thymidylate synthesis.
    Science 297: 105-107 (2002). [PMID: 12029065]
  2. Griffin, J., Roshick, C., Iliffe-Lee, E., McClarty, G.
    Catalytic mechanism of Chlamydia trachomatis flavin-dependent thymidylate synthase.
    J. Biol. Chem. 280: 5456-5467 (2005). [PMID: 15591067]
  3. Graziani, S., Bernauer, J., Skouloubris, S., Graille, M., Zhou, C. Z., Marchand, C., Decottignies, P., van Tilbeurgh, H., Myllykallio, H., Liebl, U.
    Catalytic mechanism and structure of viral flavin-dependent thymidylate synthase ThyX.
    J. Biol. Chem. 281: 24048-24057 (2006). [PMID: 16707489]
  4. Koehn, E. M., Fleischmann, T., Conrad, J. A., Palfey, B. A., Lesley, S. A., Mathews, I. I., Kohen, A.
    An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene.
    Nature 458: 919-923 (2009). [PMID: 19370033]
  5. Koehn, E. M., Kohen, A.
    Flavin-dependent thymidylate synthase: a novel pathway towards thymine.
    Arch. Biochem. Biophys. 493: 96-102 (2010). [PMID: 19643076]
  6. Mishanina, T. V., Yu, L., Karunaratne, K., Mondal, D., Corcoran, J. M., Choi, M. A., Kohen, A.
    An unprecedented mechanism of nucleotide methylation in organisms containing thyX.
    Science 351: 507-510 (2016). [PMID: 26823429]

[EC created 2003, modified 2010]