dc.contributor.author | Aučynaitė, Agota | |
dc.contributor.author | Rutkienė, Rasa | |
dc.contributor.author | Tauraitė, Daiva | |
dc.contributor.author | Meškys, Rolandas | |
dc.contributor.author | Urbonavičius, Jaunius | |
dc.date.accessioned | 2023-09-18T17:29:59Z | |
dc.date.available | 2023-09-18T17:29:59Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 1664-302X | |
dc.identifier.uri | https://etalpykla.vilniustech.lt/handle/123456789/123842 | |
dc.description.abstract | Cytosine is one of the four letters of a standard genetic code, found both in DNA and in RNA. This heterocyclic base can be converted into uracil upon the action of the well-known cytosine deaminase. Isocytosine (2-aminouracil) is an isomer of cytosine, yet the enzymes that could convert it into uracil were previously mainly overlooked. In order to search for the isocytosine deaminases we used a selection strategy that is based on uracil auxotrophy and the metagenomic libraries, which provide a random pool of genes from uncultivated soil bacteria. Several genes that encode isocytosine deaminases were found and two respective recombinant proteins were purified. It was established that both novel deaminases do not use cytosine as a substrate. Instead, these enzymes are able to convert not only isocytosine into uracil, but also 5-fluoroisocytosine into 5-fluorouracil. Our findings suggest that novel isocytosine deaminases have a potential to be efficiently used in targeted cancer therapy instead of the classical cytosine deaminases. Use of isocytosine instead of cytosine would produce fewer side effects since deaminases produced by the commensal E. coli gut flora are ten times less efficient in degrading isocytosine than cytosine. In addition, there are no known homologs of isocytosine deaminases in human cells that would induce the toxicity when 5-fluoroisocytosine would be used as a prodrug. | eng |
dc.format | PDF | |
dc.format.extent | p. 1-10 | |
dc.format.medium | tekstas / txt | |
dc.language.iso | eng | |
dc.relation.isreferencedby | PubMed | |
dc.relation.isreferencedby | Scopus | |
dc.relation.isreferencedby | Science Citation Index Expanded (Web of Science) | |
dc.source.uri | https://doi.org/10.3389/fmicb.2018.02375 | |
dc.title | Discovery of bacterial deaminases that convert 5-fluoroisocytosine Into 5-fluorouracil | |
dc.type | Straipsnis Web of Science DB / Article in Web of Science DB | |
dcterms.references | 41 | |
dc.type.pubtype | S1 - Straipsnis Web of Science DB / Web of Science DB article | |
dc.contributor.institution | Vilniaus universitetas | |
dc.contributor.institution | Vilniaus Gedimino technikos universitetas Vilniaus universitetas | |
dc.contributor.faculty | Fundamentinių mokslų fakultetas / Faculty of Fundamental Sciences | |
dc.subject.researchfield | T 005 - Chemijos inžinerija / Chemical engineering | |
dc.subject.researchfield | N 004 - Biochemija / Biochemistry | |
dc.subject.researchfield | T 008 - Medžiagų inžinerija / Material engineering | |
dc.subject.vgtuprioritizedfields | FM0202 - Ląstelių ir jų biologiškai aktyvių komponentų tyrimai / Investigations on cells and their biologically active components | |
dc.subject.ltspecializations | L105 - Sveikatos technologijos ir biotechnologijos / Health technologies and biotechnologies | |
dc.subject.en | metagenomics | |
dc.subject.en | deaminase | |
dc.subject.en | isocytosine | |
dc.subject.en | 5-fluorouracil | |
dc.subject.en | cancer therapy | |
dcterms.sourcetitle | Frontiers in microbiology | |
dc.description.volume | vol. 9 | |
dc.publisher.name | Frontiers Media SA | |
dc.publisher.city | Lausanne | |
dc.identifier.doi | 000446586100001 | |
dc.identifier.doi | 2-s2.0-85055137495 | |
dc.identifier.doi | 10.3389/fmicb.2018.02375 | |
dc.identifier.elaba | 31948033 | |