An alternative flavin-dependent mechanism for thymidylate synthesis |
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Authors: | Myllykallio Hannu Lipowski Gerard Leduc Damien Filee Jonathan Forterre Patrick Liebl Ursula |
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Institution: | Institut de Génétique et Microbiologie, CNRS UMR 8621, Université Paris-Sud, Orsay, France. hannu.myllykallio@igmors.u-psud.fr |
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Abstract: | 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 lacking thyA. 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. |
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