Applied Microbiology and Biotechnology

, Volume 74, Issue 2, pp 282–289

Thymidyl biosynthesis enzymes as antibiotic targets


  • Anatoly Chernyshev
    • Department of ChemistryUniversity of Iowa
  • Todd Fleischmann
    • Department of ChemistryUniversity of Iowa
    • Department of ChemistryUniversity of Iowa

DOI: 10.1007/s00253-006-0763-1

Cite this article as:
Chernyshev, A., Fleischmann, T. & Kohen, A. Appl Microbiol Biotechnol (2007) 74: 282. doi:10.1007/s00253-006-0763-1


The two long-known “classical” enzymes of uridyl-5-methylation, thymidylate synthase and ribothymidyl synthase, have been joined by two alternative methylation enzymes, flavin-dependent thymidylate synthase and folate-dependent ribothymidyl synthase. These two newly discovered enzymes have much in common: both contain flavin cofactors, utilize methylenetetrahydrofolate as a source of methyl group, and perform thymidylate synthesis via chemical pathways distinct from those of their classic counterparts. Several severe human pathogens (e.g., typhus, anthrax, tuberculosis, and more) depend on these “alternative” enzymes for reproduction. These and other distinctive properties make the alternative enzymes and their corresponding genes appealing targets for new antibiotics.


ThymineBiosynthesisFlavinThymidylate Synthase

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© Springer-Verlag 2007