title: Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea.
abstract: The hyperthermophilic anaerobic archaeon Pyrococcus abyssi, which lacks thymidine kinase, incorporates label from extracellular uracil, but not from thymidine, into its DNA. This implies that P. abyssi must synthesize dTMP (thymidylate), an essential precursor for DNA synthesis, de novo. However, iterative similarity searches of the three completed Pyrococcus genomes fail to detect candidate genes for canonical thymidylate synthase ThyA, suggesting the presence of alternative pathways for dTMP synthesis. Indeed, by identifying a novel class of flavin-dependent thymidylate synthases, ThyX, we have recently proven that two distinct pathways for de novo synthesis of dTMP are operational in the microbial world. While both thyX and thyA can be found in hyperthermophilic micro-organisms, the phylogenetic distribution of thyX among hyperthermophiles is wider than that of thyA. In this contribution, we discuss the differences in the distinct mechanisms of dTMP synthesis, with a special emphasis on hyperthermophilic micro-organisms.
authors.affiliation: Institut de Génétique et Microbiologie, Université de Paris-Sud, 91405 Orsay, France.
authors.forename: D
authors.initials: D
authors.lastname: Leduc
authors.forename: S
authors.initials: S
authors.lastname: Graziani
authors.forename: L
authors.initials: L
authors.lastname: Meslet-Cladiere
authors.forename: A
authors.initials: A
authors.lastname: Sodolescu
authors.forename: U
authors.initials: U
authors.lastname: Liebl
authors.forename: H
authors.initials: H
authors.lastname: Myllykallio
mesh_terms: D001105:Archaea / Q000502:physiology*; D018407:Bacterial Physiological Phenomena; D002384:Catalysis; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D005415:Flavins / Q000737:chemistry; D020745:Genome, Archaeal; D016680:Genome, Bacterial; D006358:Hot Temperature; D008957:Models, Genetic; D008958:Models, Molecular; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D019711:Pyrococcus / Q000378:metabolism; D013696:Temperature; D020124:Thermotoga maritima / Q000235:genetics; D013938:Thymidine Monophosphate / Q000096:biosynthesis* / Q000737:chemistry*; D013940:Thymidylate Synthase / Q000737:chemistry
chemical_list: D005415:Flavins; D013938:Thymidine Monophosphate; D004247:DNA; D013940:Thymidylate Synthase