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Published Online May 23, 2002
Science DOI: 10.1126/science.1072113

Reports

Submitted on March 21, 2002
Accepted on April 23, 2002

An Alternative Flavin-Dependent Mechanism for Thymidylate Synthesis

Hannu Myllykallio 1*, Gerard Lipowski 2, Damien Leduc 1, Jonathan Filee 1, Patrick Forterre 1, Ursula Liebl 2*

1 Institut de Génétique et Microbiologie, CNRS UMR 8621, Université Paris-Sud, Orsay, France.
2 Institut National de la Santé et de la Recherche Médicale (INSERM) U451-Laboratory of Optics and Biosciences, Ecole Polytechnique-ENSTA, Palaiseau, France.

* To whom correspondence should be addressed. E-mail: ursula.liebl{at}polytechnique.fr.

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 non-symbiotic 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, as ThyX activity is dependent on reduced flavin nucleotides. Our findings reveal complexity in the evolution of thymidine in modern day DNA. Since ThyX proteins are found in many pathogenic microbes, they present a target for new anti-microbial compounds.



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