Applied Microbiology and Biotechnology

, Volume 74, Issue 2, pp 282-289

First online:

Thymidyl biosynthesis enzymes as antibiotic targets

  • Anatoly ChernyshevAffiliated withDepartment of Chemistry, University of Iowa
  • , Todd FleischmannAffiliated withDepartment of Chemistry, University of Iowa
  • , Amnon KohenAffiliated withDepartment of Chemistry, University of Iowa Email author 

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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.


Thymine Biosynthesis Flavin Thymidylate Synthase