IUBMB Enzyme Nomenclature


Accepted name: thymidylate synthase (FAD)

Reaction: 5,10-methylenetetrahydrofolate + dUMP + NADPH + H+ = dTMP + tetrahydrofolate + NADP+

For diagram of reaction click here.

Other name(s): Thy1; ThyX

Systematic name: 5,10-methylenetetrahydrofolate,FADH2:dUMP C-methyltransferase

Comments: 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: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 850167-13-4


1. Myllykallio, H., Lipowski, G., Leduc, D., Filee, J., Forterre, P. and Liebl, U. An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297 (2002) 105-107. [PMID: 12029065]

2. Griffin, J., Roshick, C., Iliffe-Lee, E. and McClarty, G. Catalytic mechanism of Chlamydia trachomatis flavin-dependent thymidylate synthase. J. Biol. Chem. 280 (2005) 5456-5467. [PMID: 15591067]

3. Graziani, S., Bernauer, J., Skouloubris, S., Graille, M., Zhou, C.Z., Marchand, C., Decottignies, P., van Tilbeurgh, H., Myllykallio, H. and Liebl, U. Catalytic mechanism and structure of viral flavin-dependent thymidylate synthase ThyX. J. Biol. Chem. 281 (2006) 24048-24057. [PMID: 16707489]

4. Koehn, E.M., Fleischmann, T., Conrad, J.A., Palfey, B.A., Lesley, S.A., Mathews, I.I. and Kohen, A. An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene. Nature 458 (2009) 919-923. [PMID: 19370033]

5. Koehn, E.M. and Kohen, A. Flavin-dependent thymidylate synthase: a novel pathway towards thymine. Arch. Biochem. Biophys. 493 (2010) 96-102. [PMID: 19643076]

[EC created 2003, modified 2010]

Return to EC 2.1.1 home page
Return to EC 2.1 home page
Return to EC 2 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page