An Alternative Flavin-Dependent Mechanism for Thymidylate Synthesis

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Science  05 Jul 2002:
Vol. 297, Issue 5578, pp. 105-107
DOI: 10.1126/science.1072113

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Although deoxythymidylate cannot be provided directly by ribonucleotide reductase, the gene encoding thymidylate synthase ThyA is absent from the genomes of a large number of nonsymbiotic microbes. We show that ThyX (Thy1) proteins of previously unknown function form a large and distinct class of thymidylate synthases.ThyX has a wide but sporadic phylogenetic distribution, almost exclusively limited to microbial genomes lackingthyA. ThyX and ThyA use different reductive mechanisms, because ThyX activity is dependent on reduced flavin nucleotides. Our findings reveal complexity in the evolution of thymidine in present-day DNA. Because ThyX proteins are found in many pathogenic microbes, they present a previously uncharacterized target for antimicrobial compounds.

  • * To whom correspondence should be addressed. E-mail: hannu.myllykallio{at} (H.M.) and ursula.liebl{at} (U.L.)

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