2. Academic Validation
  3. Identification of a 2'- O-Methyluridine Nucleoside Hydrolase Using the Metagenomic Libraries

Identification of a 2'- O-Methyluridine Nucleoside Hydrolase Using the Metagenomic Libraries

  • Molecules. 2018 Nov 7;23(11):2904. doi: 10.3390/molecules23112904.
Agota Aučynaitė 1 2,  Rasa Rutkienė 3,  Daiva Tauraitė 4 5,  Rolandas Meškys 6,  Jaunius Urbonavičius 7 8
Affiliations

Affiliations

  • 1 Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania. agota.aucynaite@bchi.vu.lt.
  • 2 Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania. agota.aucynaite@bchi.vu.lt.
  • 3 Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania. rasa.rutkiene@bchi.vu.lt.
  • 4 Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania. daiva.tauraite@bchi.vu.lt.
  • 5 Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania. daiva.tauraite@bchi.vu.lt.
  • 6 Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania. rolandas.meskys@bchi.vu.lt.
  • 7 Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania. jaunius.urbonavicius@bchi.vu.lt.
  • 8 Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania. jaunius.urbonavicius@bchi.vu.lt.
PMID: 30405065 DOI: 10.3390/molecules23112904
Abstract

Ribose methylation is among the most ubiquitous modifications found in RNA. 2'-O-methyluridine is found in rRNA, snRNA, snoRNA and tRNA of Archaea, Bacteria, and Eukaryota. Moreover, 2'-O-methylribonucleosides are promising starting Materials for the production of nucleic acid-based drugs. Despite the countless possibilities of practical use for the metabolic enzymes associated with methylated nucleosides, there are very few reports regarding the metabolic fate and enzymes involved in the metabolism of 2'-O-alkyl nucleosides. The presented work focuses on the cellular degradation of 2'-O-methyluridine. A novel Enzyme was found using a screening strategy that employs Escherichia coli uracil auxotroph and the metagenomic libraries. A 2'-O-methyluridine hydrolase (RK9NH) has been identified together with an aldolase (RK9DPA)-forming a part of a probable gene cluster that is involved in the degradation of 2'-O-methylated nucleosides. The RK9NH is functional in E. coli uracil auxotroph and in vitro. The RK9NH nucleoside hydrolase could be engineered to enzymatically produce 2'-O-methylated nucleosides that are of great demand as raw Materials for production of nucleic acid-based drugs. Moreover, RK9NH nucleoside hydrolase converts 5-fluorouridine, 5-fluoro-2'-deoxyuridine and 5-fluoro-2'-O-methyluridine into 5-fluorouracil, which suggests it could be employed in Cancer therapy.

Keywords

2′-O-alkyl nucleosides; 2′-O-methyluridine; 5-fluorouracil; metagenomics; nucleoside hydrolase.

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